Tag Archives: Alzheimer’s Disease

Healing brain cells and tackling neurodegenerative diseases with nanoflowers

Leave a reply

A July 18, 2025 news item on Nanowerk describes research into a new therapeutic approach to neurodegenerative disease,

A study published in Journal of Biological Chemistry (“Neuroprotective properties of transition metal dichalcogenide nanoflowers alleviate acute and chronic neurological conditions linked to mitochondrial dysfunction”) demonstrated that nanoflowers — a type of metallic flower-shaped nanoparticle — can protect and heal brain cells by promoting the health and turnover of mitochondria, the molecular machines responsible for producing most of our cells’ energy.

These findings suggest a promising new approach to neurotherapeutics that targets the underlying mechanisms of diseases like Parkinson’s and Alzheimer’s, rather than just managing symptoms.

The study was conducted by Charles Mitchell, a doctoral student in the Texas A&M College of Agriculture and Life Sciences Department of Biochemistry and Biophysics, and research specialist Mikhail Matveyenka. Both are members in the lab of Dmitry Kurouski, associate professor and Texas A&M AgriLife Institute for Advancing Health through Agriculture researcher, who supervised the project.

“These nanoflowers look beautiful under a microscope, but what they do inside the cell is even more impressive,” Kurouski said. “By improving the health of brain cells, they help address one of the key drivers of neurodegenerative diseases that have long resisted therapeutic breakthroughs.”

…

An August 5, 2025 Texas A&M University news release (also on EurekAlert) by Ashley Vargo,which originated the news item, provides more insight into the research, Note 1: The discrepancy in the dates is likely due to the August 5, 2025 being the second issue of an earlier release; Note 2: Links have been removed,

…

Mitochondria At The Heart Of Brain Health

Mitochondria, often called the “powerhouses of the cell,” are responsible for turning food into energy the body can use. However, like any energy system, they produce some waste in the process, including elevated reactive oxygen species — unstable molecules that can damage cells if not properly managed.

To assess the therapeutic potential of nanoflowers, Kurouski’s team, which specializes in neurodegenerative diseases, tested how two nanoflowers affect neurons and supportive brain cells called astrocytes. Within 24 hours of treatment, they saw a dramatic drop in levels of reactive oxygen species, along with signs of improved mitochondrial integrity and quantity.

“Even in healthy cells, some oxidative stress is expected,” Kurouski said. “But the nanoflowers seem to fine-tune the performance of mitochondria, ultimately bringing the levels of their toxic byproducts down to almost nothing.”

Because brain health and mitochondrial function are tightly linked, Kurouski believes protecting mitochondria in brain cells could lead to meaningful improvement in brain function after damage from disease, particularly those like Parkinson’s and Alzheimer’s.

“If we can protect or restore mitochondrial health, then we’re not just treating symptoms — we’re addressing the root cause of the damage,” Kurouski said.

Extending The Findings Beyond Cell Cultures

After seeing the effects in individual cells, researchers next evaluated the nanoflowers in Caenorhabditis elegans, a well-established model organism used in neurological research, to test the effects on whole organisms.

Worms treated with one of the nanoflowers survived for days longer than their untreated counterparts, which have a typical lifespan of about 18 days. Those treated also had lower mortality during early life stages, another indication of the nanoflowers’ neuroprotective potential.

Looking forward, Kurouski plans to conduct toxicity and distribution studies in more complex animal models, a key step prior to clinical trials.

A New Path Forward For Neurotherapeutics

Despite decades of research, effective neuroprotective drugs remain elusive. Most therapies for neurodegenerative diseases rely on managing symptoms without addressing the underlying cell damage. However, Kurouski believes that, by directly targeting mitochondrial health and oxidative stress, nanoflowers could offer an innovative new approach to treatment.

His team recently worked with Texas A&M Innovation to file a patent application for the use of nanoflowers in neuroprotective treatments, and it plans to collaborate with the Texas A&M College of Medicine when it’s ready to explore the nanoflowers’ effect further for the treatment of stroke, spinal cord injuries and neurodegenerative diseases.

“We think this could become a new class of therapeutics,” Kurouski said. “We want to make sure it’s safe, effective and has a clear mechanism of action. But based on what we’ve seen so far, there’s incredible potential in nanoflowers.”

Here’s a link to and a citation for the paper,

Neuroprotective properties of transition metal dichalcogenide nanoflowers alleviate acute and chronic neurological conditions linked to mitochondrial dysfunction by Charles L. Mitchell, Mikhail Matveyenka, Dmitry Kurouski. JBC (Journal of Biological Chemistry) Volume 301, Issue 5, May 2025, 108498 DOI: https://doi.org/10.1016/j.jbc.2025.108498 Available online 9 April 2025, Version of Record 9 May 2025

This paper is open access.

Neuron survival in Alzheimer’s model dramatically improved with sugar-coated nanotherapy

Leave a reply

A May 14, 2025 news item on ScienceDaily announces research from Northwestern University (Chicago, Illinois) that could delay the progress of diseases like Alzheimer’s and amyotrophic lateral sclerosis (ALS),

Scientists at Northwestern University have developed a new approach that directly combats the progression of neurodegenerative diseases like Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).

In these devastating illnesses, proteins misfold and clump together around brain cells, which ultimately leads to cell death. The innovative new treatment effectively traps the proteins before they can aggregate into the toxic structures capable of penetrating neurons. The trapped proteins then harmlessly degrade in the body.

…

…

Caption: Labeled micrographs of human neurons exposed to amyloid-beta proteins and either left untreated (left) or treated with the new nanotherapy developed at Northwestern (right). Dead neurons are stained in red; live neurons are green. Credit: Samuel Stupp Laboratory/Northwestern University

A May 14, 2025 Northwestern University news release (also on EurekAlert) by Amanda Morris, which originated the news item, provides more detail about the work, Note: Links have been removed,

The “clean-up” strategy significantly boosted the survival of lab-grown human neurons under stress from disease-causing proteins.

Designated as an ACS [American Chemical Society] Editor’s Choice article, the study will be published on May 14 [2025] in the Journal of the American Chemical Society [JACS].

“Our study highlights the exciting potential of molecularly engineered nanomaterials to address the root causes of neurodegenerative diseases,” said Northwestern’s Samuel I. Stupp, the study’s senior author. “In many of these diseases, proteins lose their functional folded structure and aggregate to make destructive fibers that enter neurons and are highly toxic to them. 

“By trapping the misfolded proteins, our treatment inhibits the formation of those fibers at an early stage. Early stage, short amyloid fibers, which penetrate neurons, are believed to be the most toxic structures. With further work, we think this could significantly delay progression of the disease.”

A pioneer in regenerative medicine, Stupp is the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. He also is the founding director of the Center for Regenerative Nanomedicine (CRN). Zijun Gao, a Ph.D. candidate in Stupp’s laboratory, is the paper’s first author.

The Stupp group led the development and characterization of the new therapeutic materials. Co-corresponding author Zaida Alvarez — a researcher at the Institute for Bioengineering of Catalonia (IBEC) in Spain, former postdoctoral fellow in Stupp’s laboratory and current visiting scholar at CRN — led testing of the therapies in human neurons.

A sugar-coated solution

According to the World Health Organization, as many as 50 million people worldwide might have a neurodegenerative disorder. Most of these diseases are characterized by the accumulation of misfolded proteins in the brain, leading to the progressive loss of neurons. While current treatments offer limited relief, a dire need for new therapies remains.

To tackle this challenge, the researchers turned to a class of peptide amphiphiles, pioneered by the Stupp laboratory, that contain modified chains of amino acids. Peptide amphiphiles are already used in well-known pharmaceuticals including semaglutide, or Ozempic. In fact, the Northwestern investigators developed a similar molecule in 2012 that boosted insulin production.

“The advantage of peptide-based drugs is that they degrade into nutrients,” Stupp said. “The molecules in this novel therapeutic concept break down into harmless lipids, amino acids and sugars. That means there are fewer adverse side effects.”

Over the years, Stupp’s research group has designed many peptide-based materials for different therapeutic purposes. To develop a peptide amphiphile to treat neurodegenerative diseases, his team added an extra ingredient: a natural sugar called trehalose.

“Trehalose is naturally occurring in plants, fungi and insects,” Gao said. “It protects them from changing temperatures, especially dehydration and freezing. Others have discovered trehalose can protect many biological macromolecules, including proteins. So, we wanted to see if we could use it to stabilize misfolded proteins.”

Instability is key

When added to water, the peptide amphiphiles self-assembled into nanofibers coated with trehalose. Surprisingly, the trehalose destabilized the nanofibers. Although it seems counterintuitive, this decreased stability exhibited a beneficial effect.

By themselves, the nanofibers are strong and well-ordered — and resistant to rearranging their structure. That makes it more difficult for other molecules, like misfolded proteins, to integrate into the fibers. Less stable fibers, on the other hand, became more dynamic — and more likely to find and interact with toxic proteins.

“Unstable assemblies of molecules are very reactive,” Stupp said. “They want to interact with and bond to other molecules. If the nanofibers were stable, they would happily ignore everything around them.”

Searching for stability, the nanofibers bonded to amyloid-beta proteins, a key culprit implicated in Alzheimer’s disease. But the nanofibers didn’t just stop the amyloid-beta proteins from clumping together. The nanofibers fully incorporated the proteins into their own fibrous structures — permanently trapping them into stable filaments. 

“Then, it’s no longer a peptide amphiphile fiber anymore,” Stupp said. “But a new hybrid structure comprising both the peptide amphiphile and the amyloid-beta protein. That means the nasty amyloid-beta proteins, which would have formed amyloid fibers, are trapped. They can no longer penetrate the neurons and kill them. It’s like a clean-up crew for misfolded proteins.

“This is a novel mechanism to tackle progression of neurodegenerative diseases, such as Alzheimer’s, at an earlier stage. Current therapies rely on the production of antibodies for well-formed amyloid fibers.”

Improving neuron survival

To assess the therapeutic potential of the new approach, the scientists conducted laboratory tests using human neurons derived from stem cells. The results showed the trehalose-coated nanofibers significantly improved the survival of both motor and cortical neurons when exposed to the toxic amyloid-beta protein.

Stupp says the novel approach of using unstable nanofibers to trap proteins offers a promising avenue for developing new and effective therapies for Alzheimer’s, ALS and other neurodegenerative conditions. Much like cancer treatments combine multiple therapies — like chemotherapy and surgery or hormone therapy and radiation — Stupp said the nanotherapy might be most effective when combined with other treatments.

“Our therapy might work best when targeting diseases at an earlier stage — before aggregated proteins enter cells,” Stupp said. “But it’s challenging to diagnose these diseases at early stages. So, it could be combined with therapies that target later-stage symptoms of the disease. Then, it could be a double whammy.”

Here’s a link to and a citation for the paper,

Supramolecular Copolymerization of Glycopeptide Amphiphiles and Amyloid Peptides Improves Neuron Survival by Zijun Gao, Ruomeng Qiu, Dhwanit R. Dave, Palash Chandravanshi, Gisele P. Soares, Cara S. Smith, J. Alberto Ortega, Liam C. Palmer, Zaida Álvarez, Samuel I. Stupp. Journal of the American Chemical Society 2025, 147, 21, 17710–17724 DOI: https://doi.org/10.1021/jacs.5c00105 Published May 14, 2025 Copyright © 2025 American Chemical Society

This paper is open access.

Organoids with four different types of brain cells from the University of Saskatchewan (USask)

Leave a reply
While a USask-designed “mini-brain” synthetic organoid might look like a tiny wad of chewing gum, it could be a gamechanger for Alzheimer’s research (credit: USask/David Stobbe)

A May 14, 2024 news item on ScienceDaily announces research from the University of Saskatchewan that could improve diagnosis and treatment for Alzheimer’s disease,

Using an innovative new method, a University of Saskatchewan (USask) researcher is building tiny pseudo-organs from stem cells to help diagnose and treat Alzheimer’s.

When Dr. Tyler Wenzel (PhD) first came up with the idea of building a miniature brain from stem cells, he never could have predicted how well his creations would work.

Now, Wenzel’s “mini-brain” could revolutionize the way Alzheimer’s and other brain-related diseases are diagnosed and treated.

“Never in our wildest dreams did we think that our crazy idea would work,” he said. “These could be used as a diagnostic tool, built from blood.”

…

A May 14, 2024 University of Saskatchewan news release (also on EurekAlert), which originated the news item, provides more technical details, Note: A link has been removed,

Wenzel, a postdoctoral fellow in the College of Medicine’s Department of Psychiatry, developed the idea for the “mini-brain” – or more formally, a one-of-a-kind cerebral organoid model – while working under the supervision of Dr. Darrell Mousseau (PhD).

Human stem cells can be manipulated to develop into practically any other cell in the body. Using stem cells taken from human blood, Wenzel was able to create a tiny artificial organ – roughly three millimetres across and resembling visually what Wenzel described as a piece of chewed gum someone has tried to smooth out again.

These “mini-brains” are built by creating stem cells from a blood sample, and then transforming these stem cells into functioning brain cells. Using small synthetic organoids for research is not a novel concept – but the “mini-brains” developed in Wenzel’s lab are unique. As outlined in Wenzel’s recent published article in Frontiers of Cellular Neuroscience, the brains from Wenzel’s lab are comprised of four different types of brain cells while most brain organoids are comprised of only neurons.

In testing, Wenzel’s “mini-brains” more accurately reflect a fully-fledged adult human brain, so they can be used to more closely examine neurological conditions of adult patients, such as Alzheimer disease.

And for those “mini-brains” created from the stem cells of individuals who have Alzheimer’s, Wenzel determined that the artificial organ displayed the pathology of Alzheimer’s – just on a smaller scale.

“If stem cells have the capacity to become any cell in the human body, the question then came ‘could we create something that resembles an entire organ?’” Wenzel said. “While we were developing it, I had the crazy idea that if these truly are human brains, if a patient had a disease like Alzheimer’s and we grew their ‘mini-brain,’ in theory that tiny brain would have Alzheimer’s.”

Wenzel said this technology has the potential to change the way health services are provided to those with Alzheimer’s, particularly in rural and remote communities. This groundbreaking research has already received support from the Alzheimer Society of Canada.

If Wenzel and his colleagues can create a consistent way to diagnose and treat neurological conditions like Alzheimer’s using only a small blood sample – which has a relatively long shelf life and can be couriered – instead of requiring patients to travel to hospitals or specialized clinics, it could be a tremendous resource savings for the healthcare system and a burden off of patients.

“In theory, if this tool works the way we think it does, we could just get a blood sample shipped from La Loche or La Ronge to the university and diagnose you like that,” he said.

The early proof-of-concept work on the “mini-brains” has been extremely promising – which means the next step for Wenzel is expanding the testing to a larger pool of patients.

The researchers are also interested in trying to expand the scope of the “mini-brain” research. According to Wenzel, if they can confirm the “mini-brains” accurately reflect other brain diseases or neurological conditions, they could potentially be used to speed up diagnoses or test the efficacy of drugs on patients.

As an example, Wenzel pointed to the substantial wait times to see a psychiatrist in Saskatchewan. If the “mini-brains” could be used to test which antidepressant works best on a patient suffering from depression, it could dramatically reduce the time required to see a doctor and receive a prescription.

A former high school science teacher who made the move into the world of research and academia, Wenzel said it’s the “nature of research” to come up with a hypothesis and hit close to the mark in an experiment that excites him his work.

The astounding success of the early “mini-brains,” however, has been so staggering that Wenzel admitted he still struggles to wrap his own brain around it.

“I’m still in disbelief, but it’s also extremely motivating that something like this happened,” Wenzel said. “It gives me something that I think will impact society and have actual relevance and create some change … it has a strong potential to shift the landscape of medicine.”

Here’s a link to and a citation for the paper,

Brain organoids engineered to give rise to glia and neural networks after 90 days in culture exhibit human-specific proteoforms by Tyler J. Wenzel, Darrell D. Mousseau. Front. Cell. Neurosci., Volume 18 – 2024 DOI: https://doi.org/10.3389/fncel.2024.1383688 Published: 08 May 2024

This paper is open access.

Reducing toxicity of Alzheimer’s proteins with graphene oxide

Leave a reply

Nobody really knows what causes Alzheimer’s disease (a form of dementia) so researchers continue to investigates the cause(s) and, also, possible remedies. An October 4, 2023 news item on ScienceDaily announces some of the latest research,

A probable early driver of Alzheimer’s disease is the accumulation of molecules called amyloid peptides. These cause cell death, and are commonly found in the brains of Alzheimer’s patients. Researchers at Chalmers University of Technology, Sweden, have now shown that yeast cells that accumulate these misfolded amyloid peptides can recover after being treated with graphene oxide nanoflakes.

…

An October 4, 2023 Chalmers University of Technology press release (also received via email and on EurekAlert) by Susanne Nilsson Lindh & Johanna Wilde, which originated the news item, delves into the topic,

Alzheimer’s disease is an incurable brain disease, leading to dementia and death, that causes suffering for both the patients and their families. It is estimated that over 40 million people worldwide are living with the disease or a related form of dementia. According to Alzheimer’s News Today, the estimated global cost of these diseases is one percent of the global gross domestic product.

Misfolded amyloid-beta peptides, Aβ peptides, that accumulate and aggregate in the brain, are believed to be the underlying cause of Alzheimer’s disease. They trigger a series of harmful processes in the neurons (brain cells) – causing the loss of many vital cell functions or cell death, and thus a loss of brain function in the affected area. To date, there are no effective strategies to treat amyloid accumulation in the brain.

Researchers at Chalmers University of Technology have now shown that treatment with graphene oxide leads to reduced levels of aggregated amyloid peptides in a yeast cell model.

“This effect of graphene oxide has recently also been shown by other researchers, but not in yeast cells”, says Xin Chen, Researcher in Systems Biology at Chalmers and first author of the study. “Our study also explains the mechanism behind the effect. Graphene oxide affects the metabolism of the cells, in a way that increases their resistance to misfolded proteins and oxidative stress. This has not been previously reported.”

Investigating the mechanisms using baker’s yeast affected by Alzheimer’s disease
In Alzheimer’s disease, the amyloid aggregates exert their neurotoxic effects by causing various cellular metabolic disorders, such as stress in the endoplasmic reticulum – a major part of the cell, in which many of its proteins are produced. This can reduce cells’ ability to handle misfolded proteins, and consequently increase the accumulation of these proteins.

The aggregates also affect the function of the mitochondria, the cells’ powerhouses. Therefore, the neurons are exposed to increased oxidative stress (reactive molecules called oxygen radicals, which damage other molecules); something to which brain cells are particularly sensitive.

The Chalmers researchers have conducted the study by a combination of protein analysis (proteomics) and follow-up experiments. They have used baker’s yeast, Saccharomyces cerevisiae, as an in vivo model for human cells. Both cell types have very similar systems for controlling protein quality. This yeast cell model was previously established by the research group to mimic human neurons affected by Alzheimer’s disease.

“The yeast cells in our model resemble neurons affected by the accumulation of amyloid-beta42, which is the form of amyloid peptide most prone to aggregate formation”, says Xin Chen. “These cells age faster than normal, show endoplasmic reticulum stress and mitochondrial dysfunction, and have elevated production of harmful reactive oxygen radicals.”

High hopes for graphene oxide nanoflakes
Graphene oxide nanoflakes are two-dimensional carbon nanomaterials with unique properties, including outstanding conductivity and high biocompatibility. They are used extensively in various research projects, including the development of cancer treatments, drug delivery systems and biosensors.

The nanoflakes are hydrophilic (water soluble) and interact well with biomolecules such as proteins. When graphene oxide enters living cells, it is able to interfere with the self-assembly processes of proteins.

“As a result, it can hinder the formation of protein aggregates and promote the disintegration of existing aggregates”, says Santosh Pandit, Researcher in Systems Biology at Chalmers and co-author of the study. “We believe that the nanoflakes act via two independent pathways to mitigate the toxic effects of amyloid-beta42 in the yeast cells.”

In one pathway, graphene oxide acts directly to prevent amyloid-beta42 accumulation. In the other, graphene oxide acts indirectly by a (currently unknown) mechanism, in which specific genes for stress response are activated. This increases the cell’s ability to handle misfolded proteins and oxidative stress.

How to treat Alzheimer’s patients is still a question for the future. However, according to the research group at Chalmers, graphene oxide holds great potential for future research in the field of neurodegenerative diseases. The research group has already been able to show that treatment with graphene oxide also reduces the toxic effects of protein aggregates specific to Huntington’s disease in a yeast model.

“The next step is to investigate whether it is possible to develop a drug delivery system based on graphene oxide for Alzheimer’s disease.” says Xin Chen. “We also want to test whether graphene oxide has beneficial effects in additional models of neurodegenerative diseases, such as Parkinson’s disease.”

More about: proteins and peptides
Proteins and peptides are fundamentally the same type of molecule and are made up of amino acids. Peptide molecules are smaller – typically containing less than 50 amino acids – and have a less complicated structure. Proteins and peptides can both become deformed if they fold in the wrong way during formation in the cell. When many amyloid-beta peptides accumulate in the brain, the aggregates are classified as proteins.

Here’s a link to and a citation for the paper,

Graphene Oxide Attenuates Toxicity of Amyloid-β Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response by Xin Chen, Santosh Pandit, Lei Shi, Vaishnavi Ravikumar, Julie Bonne Køhler, Ema Svetlicic, Zhejian Cao, Abhroop Garg, Dina Petranovic, Ivan Mijakovic. Advanced Functional Materials Volume 33, Issue 45 November 2, 2023 2304053 DOI: https://doi.org/10.1002/adfm.202304053 First published online: 07 July 2023

This paper is open access.

Get your curcumin delivered by nanoparticles

Leave a reply

Curcumin is a constituent of turmeric (used in cooking and as a remedy in Ayurvedic medicine). It’s been a while since I’ve stumbled across a curcumin story (scientists have been trying to find a way to exploit its therapeutic qualities for years). The latest news comes from Australia, which is a little unexpected as most of the ‘curcumin research stories’ previously on this blog have come from India.

A March 5, 2020 news item on ScienceDaily announces new research on curcumin therapeutic possibilities,

For years, curry lovers have sworn by the anti-inflammatory properties of turmeric, but its active compound, curcumin, has long frustrated scientists hoping to validate these claims with clinical studies.

The failure of the body to easily absorb curcumin has been a thorn in the side of medical researchers seeking scientific proof that curcumin can successfully treat cancer, heart disease, Alzheimer’s and many other chronic health conditions.

Now, researchers from the University of South Australia (UniSA), McMaster University in Canada and Texas A&M University have shown that curcumin can be delivered effectively into human cells via tiny nanoparticles.

Over three years ago on December 2, 2016, researchers from McMaster University made this video about Alzheimer’s and curcumin research available,

From the McMaster University, Centre for Health Economics & Policy Analysis, December 2, 2016 news webpage,

This video investigates the therapeutic potential of curcumin, a substance found in turmeric, to prevent Alzheimer’s disease. The information presented in this video has integrated research including in vitro studies that aimed to observe the influence of curcumin based interventions in the neuropathology of Alzheimer’s disease. From mechanisms for neurogenesis to the disintegration of beta amyloid plaques, this video highlights that there are many pathways by which curcumin can elicit its effects. However, there are currently not enough human trials to support the mouse-model studies for turmeric’s ability to prevent Alzheimer’s.

Back to the latest work, a March 5, 2020 UniSA press release (also on EurekAlert), which originated the news item, describes curcumin research that focuses on STI’s (sexually transmitted infections), also mentioned is earlier work on Alzheimer’s Disease,

Sanjay Garg, a professor of pharmaceutical science at UniSA, and his colleague Dr Ankit Parikh are part of an international team that has developed a nano formulation which changes curcumin’s behaviour to increase its oral bioavailability by 117 per cent.

The researchers have shown in animal experiments that nanoparticles containing curcumin not only prevents cognitive deterioration but also reverses the damage. This finding paves the way for clinical development trials for Alzheimer’s.

Co-author Professor Xin-Fu Zhou, a UniSA neuroscientist, says the new formulation offers a potential solution for Alzheimer’s disease.

“Curcumin is a compound that suppresses oxidative stress and inflammation, both key pathological factors for Alzheimer’s, and it also helps remove amyloid plaques, small fragments of protein that clump together in the brains of Alzheimer disease patients,” Prof Zhou says.

The same delivery method is now being tested to show that curcumin can also prevent the spread of genital herpes.

“To treat genital herpes (HSV-2) you need a form of curcumin that is better absorbed, which is why it needs to be encapsulated in a nano formulation,” Prof Garg says.

“Curcumin can stop the genital herpes virus, it helps in reducing the inflammation and makes it less susceptible to HIV and other STIs,” Prof Garg says.

Women are biologically more vulnerable to genital herpes as bacterial and viral infections in the female genital tract (FGT) impair the mucosal barrier. Curcumin, however, can minimize genital inflammation and control against HSV-2 infection, which would assist in the prevention of HIV infection in the FGT.

Here’s a link to and a citation for the latest paper,

Curcumin Can Decrease Tissue Inflammation and the Severity of HSV-2 Infection in the Female Reproductive Mucosa by Danielle Vitali, Puja Bagri, Jocelyn M. Wessels, Meenakshi Arora, Raghu Ganugula, Ankit Parikh, Talveer Mandur, Allison Felker, Sanjay Garg, M.N.V. Ravi Kumar, and Charu Kaushic. Int. J. Mol. Sci. 2020, 21(1), 337; DOI: https://doi.org/10.3390/ijms21010337 Published: 4 January 2020

This is an open access paper and is part of the journal’s Special Issue Curcumin in Health and Disease: New Knowledge)

For anyone interested in the earlier work on Alzheimer’s Disease, here are links to two papers that were published in 2018 by a team led by Sanjay Garg,

Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability by Ankit Parikh, Krishna Kathawala, Yunmei Song, Xin-Fu Zhou & Sanjay Garg. Drug Delivery and Translational Research volume 8, pages 1389–1405 (2018) DOI: https://doi.org/10.1007/s13346-018-0543-3 Issue Date: October 2018

Curcumin-loaded self-nanomicellizing solid dispersion system: part II: in vivo safety and efficacy assessment against behavior deficit in Alzheimer disease by Ankit Parikh, Krishna Kathawala, Jintao Li, Chi Chen, Zhengnan Shan, Xia Cao, Xin-Fu Zhou & Sanjay Garg. Drug Delivery and Translational Research volume 8, pages 1406–1420 (2018) DOI: https://doi.org/10.1007/s13346-018-0570-0 Issue Date: October 2018

Neither of these paper is open access but you can gain access by contacting sanjay.garg@unisa.edu.au

This looks like exciting work, bearing in mind the latest curcumin research on an STI was performed on female mice. As for the Alzheimer’s papers, that curcumin research was also performed on animals, presumably mice. As the press release noted, “This finding paves the way for clinical development trials for Alzheimer’s.” Oddly, there’s no mention of clinical trials for STI’s.

Repairing brain circuits using nanotechnology

Leave a reply

A July 30, 2019 news item on Nanowerk announces some neuroscience research (they used animal models) that could prove helpful with neurodegenerative diseases,

Working with mouse and human tissue, Johns Hopkins Medicine researchers report new evidence that a protein pumped out of some — but not all — populations of “helper” cells in the brain, called astrocytes, plays a specific role in directing the formation of connections among neurons needed for learning and forming new memories.

Using mice genetically engineered and bred with fewer such connections, the researchers conducted proof-of-concept experiments that show they could deliver corrective proteins via nanoparticles to replace the missing protein needed for “road repairs” on the defective neural highway.

Since such connective networks are lost or damaged by neurodegenerative diseases such as Alzheimer’s or certain types of intellectual disability, such as Norrie disease, the researchers say their findings advance efforts to regrow and repair the networks and potentially restore normal brain function.

…

A July 30, 2019 Johns Hopkins University School of Medicine news release (also on EurekAlert) provides more detail about the work (Note: A link has been removed),

“We are looking at the fundamental biology of how astrocytes function, but perhaps have discovered a new target for someday intervening in neurodegenerative diseases with novel therapeutics,” says Jeffrey Rothstein, M.D., Ph.D., the John W. Griffin Director of the Brain Science Institute and professor of neurology at the Johns Hopkins University School of Medicine.

“Although astrocytes appear to all look alike in the brain, we had an inkling that they might have specialized roles in the brain due to regional differences in the brain’s function and because of observed changes in certain diseases,” says Rothstein. “The hope is that learning to harness the individual differences in these distinct populations of astrocytes may allow us to direct brain development or even reverse the effects of certain brain conditions, and our current studies have advanced that hope.”

In the brain, astrocytes are the support cells that act as guides to direct new cells, promote chemical signaling, and clean up byproducts of brain cell metabolism.

Rothstein’s team focused on a particular astrocyte protein, glutamate transporter-1, which previous studies suggested was lost from astrocytes in certain parts of brains with neurodegenerative diseases. Like a biological vacuum cleaner, the protein normally sucks up the chemical “messenger” glutamate from the spaces between neurons after a message is sent to another cell, a step required to end the transmission and prevent toxic levels of glutamate from building up.

When these glutamate transporters disappear from certain parts of the brain — such as the motor cortex and spinal cord in people with amyotrophic lateral sclerosis (ALS) — glutamate hangs around much too long, sending messages that overexcite and kill the cells.

To figure out how the brain decides which cells need the glutamate transporters, Rothstein and colleagues focused on the region of DNA in front of the gene that typically controls the on-off switch needed to manufacture the protein. They genetically engineered mice to glow red in every cell where the gene is activated.

Normally, the glutamate transporter is turned on in all astrocytes. But, by using between 1,000- and 7,000-bit segments of DNA code from the on-off switch for glutamate, all the cells in the brain glowed red, including the neurons. It wasn’t until the researchers tried the largest sequence of an 8,300-bit DNA code from this location that the researchers began to see some selection in red cells. These red cells were all astrocytes but only in certain layers of the brain’s cortex in mice.

Because they could identify these “8.3 red astrocytes,” the researchers thought they might have a specific function different than other astrocytes in the brain. To find out more precisely what these 8.3 red astrocytes do in the brain, the researchers used a cell-sorting machine to separate the red astrocytes from the uncolored ones in mouse brain cortical tissue, and then identified which genes were turned on to much higher than usual levels in the red compared to the uncolored cell populations. The researchers found that the 8.3 red astrocytes turn on high levels of a gene that codes for a different protein known as Norrin.

Rothstein’s team took neurons from normal mouse brains, treated them with Norrin, and found that those neurons grew more of the “branches” — or extensions — used to transmit chemical messages among brain cells. Then, Rothstein says, the researchers looked at the brains of mice engineered to lack Norrin, and saw that these neurons had fewer branches than in healthy mice that made Norrin.

In another set of experiments, the research team took the DNA code for Norrin plus the 8,300 “location” DNA and assembled them into deliverable nanoparticles. When they injected the Norrin nanoparticles into the brains of mice engineered without Norrin, the neurons in these mice began to quickly grow many more branches, a process suggesting repair to neural networks. They repeated these experiments with human neurons too.

Rothstein notes that mutations in the Norrin protein that reduce levels of the protein in people cause Norrie disease — a rare, genetic disorder that can lead to blindness in infancy and intellectual disability. Because the researchers were able to grow new branches for communication, they believe it may one day be possible to use Norrin to treat some types of intellectual disabilities such as Norrie disease.

For their next steps, the researchers are investigating if Norrin can repair connections in the brains of animal models with neurodegenerative diseases, and in preparation for potential success, Miller [sic] and Rothstein have submitted a patent for Norrin.

Here’s a link to and a citation for the paper,

Molecularly defined cortical astroglia subpopulation modulates neurons via secretion of Norrin by Sean J. Miller, Thomas Philips, Namho Kim, Raha Dastgheyb, Zhuoxun Chen, Yi-Chun Hsieh, J. Gavin Daigle, Malika Datta, Jeannie Chew, Svetlana Vidensky, Jacqueline T. Pham, Ethan G. Hughes, Michael B. Robinson, Rita Sattler, Raju Tomer, Jung Soo Suk, Dwight E. Bergles, Norman Haughey, Mikhail Pletnikov, Justin Hanes & Jeffrey D. Rothstein. Nature Neuroscience volume 22, pages741–752 (2019) DOI: https://doi.org/10.1038/s41593-019-0366-7 Published: 01 April 2019 Issue Date: May 2019

This paper is behind a paywall.

Structure of tunneling nanotubes (TNTs) challenges the dogma of the cell

Leave a reply

There is a video that accompanies the news but I strongly advise reading the press release first, unless you already know a lot about cells and tunneling nanotubes.

A January 30, 2019 Institut Pasteur press release (also on EurekAlert but published Jan.31, 2019) announces the work,

Cells in our bodies have the ability to speak with one another much like humans do. This communication allows organs in our bodies to work synchronously, which in turn, enables us to perform the remarkable range of tasks we meet on a daily basis. One of this mean of communication is ‘tunneling nanotubes’ or TNTs. In an article published in Nature Communications, researchers from the Institut Pasteur leaded by Chiara Zurzolo discovered, thanks to advanced imaging techniques, that the structure of these nanotubes challenged the very concept of cell.

As their name implies, TNTs are tiny tunnels that link two (or more cells) and allow the transport of a wide variety of cargoes between them, including ions, viruses, and entire organelles. Previous research by the same team (Membrane Traf?c and Pathogenesis Unit) at the Institut Pasteur have shown that TNTs are involved in the intercellular spreading of pathogenic amyloid proteins involved in Alzheimer and Parkinson’s disease. This led researchers to propose that they serve as a major avenue for the spreading of neurodegenerative diseases in the brain and therefore represent a novel therapeutic target to stop the progression of these incurable diseases. TNTs also appear to play a major role in cancer resistance to therapy. But as scientists still know very little about TNTs and how they relate or differ from other cellular protrusions such as filopodia, they decided to pursue their research to deal with these tiny tubular connections in depth.

The dogma of cell unit questioned

A better understanding of these tiny tubular connections is therefore required as TNTs might have tremendous implications in human health and disease. Addressing this issue has been very difficult due to the fragile and transitory nature of these structures, which do not survive classical microscopic techniques. In order to overcome these obstacles, researchers combined various state-of-the-art electron microscopy approaches, and imaged TNTs at below-freezing temperatures.

Using this imaging strategy, researchers were able to decipher the structure of TNTs in high detail. Specifically, they show that most TNTs – previously shown to be single connections – are in fact made up of multiple, smaller, individual tunneling nanotubes (iTNTs). Their images also show the existence of thin wires that connect iTNTs, which could serve to increase their mechanical stability. They demonstrate the functionality of iTNTs by showing the transport of organelles using time-lapse imaging. Finally, researchers employed a type of microscopy known as ‘FIB-SEM’ to produce 3D images with sufficient resolution to clearly identify that TNTs are ‘open’ at both ends, and thus create continuity between two cells. “This discovery challenges the dogma of cells as individual units, showing that cells can open up to neighbors and exchange materials without a membrane barrier” explains Chiara Zurzolo, head of the Membrane Traf?c and Pathogenesis Unit at the Institut Pasteur.

A news step in cell-to-cell communication decoding

By applying an imaging work-flow that improves upon, and avoids, previous limitations of tools used to study the anatomy of TNTs, researchers provide the first structural description of TNTs. Importantly, they provide the absolute demonstration that these are novel cellular organelles with a defined structure, very different from known cell protrusions. “The description of the structure allows the understanding of the mechanisms involved in their formation and provides a better comprehension of their function in transferring material directly between (the cytosol of) two connected cells” says Chiara Zurzolo. Furthermore, their strategy, which preserves these delicate structures, will be useful for studying the role TNTs play in other physiological and pathological conditions

This work is an essential step toward understanding cell-to-cell communication via TNTs and lays the groundwork for investigations into their physiological functions and their role in spreading of particles linked to diseases such as viruses, bacteria, and misfolded proteins.

The researchers have kindly produced a version of the video in English,

Here’s a link to and a citation for the paper,

Correlative cryo-electron microscopy reveals the structure of TNTs in neuronal cells by Anna Sartori-Rupp, Diégo Cordero Cervantes, Anna Pepe, Karine Gousset, Elise Delage, Simon Corroyer-Dulmont, Christine Schmitt, Jacomina Krijnse-Locker & Chiara Zurzolo. Nature Communications volume 10, Article number: 342 (2019) DOI https://doi.org/10.1038/s41467-018-08178-7 Published 21 January 2019

This paper is open access.

Science events and an exhibition concerning wind in the Vancouver (Canada) area for July 2019 and beyond

Leave a reply

it’s not quite the bumper crop of science events that took place in May 2019, which may be a good thing if you’re eager to attend everything. First, here are the events and then, the exhibition.

Nerd Nite at the Movies

On July 10, 2019, a new series is being launched at the Vancouver International Film Festival (VIFF) Centre. Here’s the description from the Nerd Nite Vancouver SciFact vs SciFi: Nerd Nite Goes to the Movies event page,

SciFact vs SciFiction: Nerd Nite Goes to the Movies v1. Animal

This summer we’re trying something a little different. Our new summer series of talks – a collaboration between Nerd Nite and VIFF – examines the pseudo-science propagated by Hollywood, and seeks to sift real insights from fake facts, in a fun, playful but peer-approved format. Each show will feature clips from a variety of movies on a science theme with a featured scientist on hand all done Nerd Nite style with drinks! We begin with biology, and our first presenter is Dr Carin Bondar.

Dr Bondar has been the host of Science Channel’s Outrageous Acts of Science, and she’s the author of several books including “Wild Moms: The Science Behind Mating in the Animal Kingdom”. Tonight she’ll join Kaylee [Byers] and Michael [Unger] from Nerd Nite to discuss the sci-facts in a variety of clips from cinema. We’ll be discussing the science in Planet of the Apes, The Birds, Arachnophobia, Snakes on a Plane, and more!

When: July 10 [2019]
Where: Vancouver International Film Centre
When: 7:30 – 8:30 – This talk will be followed by a screening of Alfred Hitchcock’s classic The Birds (9pm). Double bill price: $20
Tickets: Here!

The VIFF Centre’s SciFact vs SciFi: Animals According to Hollywood event page has much the same information plus this,

SciFact vs SciFi: Nerd Nite Goes to the Movies continues:

July 31 [2019] – Dr. Douglas Scott: The Universe According to Hollywood
Aug 14 [2019] – Mika McKinnon: Disaster According to Hollywood
Aug 28 [2019] – Greg Bole: Evolution According to Hollywood

This series put me in mind what was then the New York-based, ‘Science Goes to the Movies’. I first mentioned this series in a March 10, 2016 posting and it seems that since then, the series has lost a host and been embraced by public television (in the US). You can find the latest incarnation of Science Goes To The Movies here.

Getting back to Vancouver, no word as to which movies will accompany these future talks. If I had a vote, I’d love to see Gattaca accompany any talk on genetics.

That last sentence is both true and provides a neat segue to the next event.

Genetics at the Vancouver Public Library (VPL)

Coming up on July 23, 2019, a couple of graduate students at the University of British Columbia will be sharing some of the latest information on genetics. From the VPL events page,

Curiosities of the Natural World: Genetics – the Future of Medicine

Tuesday, July 23, 2019 (7:00 pm – 8:30 pm)
Central Library
Description

Since their discovery over a century ago, diabetes, multiple sclerosis, and Alzheimer’s have seemed like diseases without a cure. The advent of genetic treatments and biomarkers are changing the outcomes and treatments of these once impossible-to-treat conditions.

UBC researchers, Adam Ramzy and Maria-Elizabeth Baeva discuss the potential of genetic therapies for diabetes, and new biomarkers and therapeutics for Alzheimer ’s disease and multiple sclerosis.

This program is part of the Curiosities of the Natural World series in partnership with UBC Let’s Talk Science, the UBC Faculty of Science, and the UBC Public Scholars Initiative

Suitable for: Adults
Seniors

…

Additional Details:
Alma VanDusen and Peter Kaye Rooms, Lower Level

It’s hard to know how to respond to this as I loathe anything that has ‘future of medicine’ in it. Isn’t there always going to ***be*** ‘a’ future with medicine in it?

Also, there is at least one cautionary tale about this new era of ‘genetic medicine’: Glybera is a gene therapy that worked for people with a rare genetic disease. It is a **treatment**, the only one, and it is no longer available.

Kelly Crowe in a November 17, 2018 article for the CBC (Canadian Broadcasting Corporation) news writes about Glybera,

It is one of this country’s great scientific achievements.

The first drug ever approved that can fix a faulty gene.

It’s called Glybera, and it can treat a painful and potentially deadly genetic disorder with a single dose — a genuine made-in-Canada medical breakthrough.

But most Canadians have never heard of it.

A team of researchers at the University of British Columbia spent decades developing the treatment for people born with a genetic mutation that causes lipoprotein lipase disorder (LPLD).

LPLD affects communities in the Saguenay region of northeastern Quebec at a higher rate than anywhere else in the world.

…

Glybera was never sold in North America and was available in Europe for just two years, beginning in 2015. During that time, only one patient received the drug. Then it was abandoned by the company that held its European licensing rights.

The problem was the price.

The world’s first gene therapy, a remarkable discovery by a dedicated team of scientists who came together in a Vancouver lab, had earned a second, more dubious distinction:

The world’s most expensive drug.

…

It cost $1M for a single treatment and that single treatment is good for at least 10 years.

Pharmaceutical companies make their money from repeated use of their medicaments and Glybera required only one treatment so the company priced it according to how much they would have gotten for repeated use, $100,000 per year over a 10 year period. The company was not able to persuade governments and/or individuals to pay the cost.

In the end, 31 people got the treatment, most of them received it for free through clinical trials.

Crowe has written an exceptionally good story (November 17, 2018 article) about Glybera and I encourage you to read in its entirety. I warn you it’s heartbreaking.

I wrote about money and genetics in an April 26, 2019 posting (Gene editing and personalized medicine: Canada). Scroll down to the subsection titled ‘Cost/benefit analysis’ for a mention of Goldman Sachs, an American global investment banking, securities and investment management firm, and its conclusion that personalized medicine is not a viable business model. I wonder if part of their analysis included the Glybera experience.

Getting back to the July 23, 2019 talk at the VPL’s central branch, I have no doubt the researchers will be discussing some exciting work but the future might not be as rosy as one might hope.

I wasn’t able to find much information about either Adan Ramzy or Maria-Elizabeth Baeva. There’s this for Ramzy (scroll down to Class of 2021) and this for Baeva (scroll down to Scholarships).

WINDS from June 22 to September 29, 2019

This show or exhibition is taking place in New Westminster (part of the Metro Vancouver area) at the Anvil Centre’s New Media Gallery. From the Anvil Centre’s WINDS event page,

WINDS
New Media Gallery Exhibition
June 22  – September 29
Opening Reception + Artist Talk  is on June 21st at 6:30pm
 
Chris Welsby (UK)
Spencer Finch (UK)
David Bowen (USA)
Nathalie Miebach (Germany/USA)
 
Our summer exhibition features four exciting, multi-media installations by four international artists from UK and USA.  Each artist connects with the representation, recreation and manifestation of wind through physical space and time.  Each suggests how our perception and understanding of wind can be created through pressure, sound, data, pattern, music and motion and then further appreciated in poetic or metaphoric ways that might connect us with how the wind influences language, imagination or our understanding of historic events.
 
All the artists use sound as a key element ; to emphasize or recreate the sonic experience of different winds and their effects, to trigger memory or emotion, or to heighten certain effects that might prompt the viewer to consider significant philosophical questions. Common objects are used in all the works; discarded objects, household or readymade objects and everyday materials; organic, synthetic, natural and manmade. The viewer will find connections with past winds and events both recent and distant.  There is an attempt to capture or allude to a moment in time which brings with it suggestions of mortality,  thereby transforming the works into poignant memento-mori.

Dates
June 22 – September 29, 2019

Price
Complimentary

Location
777 Columbia Street. New Media Gallery.

The New Media Gallery’s home page features ‘winds’ (yes, it’s all in lower case),

Landscape and weather have long shared an intimate connection with the arts.  Each of the works here is a landscape: captured, interpreted and presented through a range of technologies. The four artists in this exhibition have taken, as their material process, the movement of wind through physical space & time. They explore how our perception and understanding of landscape can be interpreted through technology. 

These works have been created by what might be understood as a sort of scientific method or process that involves collecting data, acute observation, controlled experiments and the incorporation of measurements and technologies that control or collect motion, pressure, sound, pattern and the like. The artists then take us in other directions; allowing technology or situations to render visible that which is invisible, creating and focussing on peculiar or resonant qualities of sound, light or movement in ways that seem to influence emotion or memory, dwelling on iconic places and events, or revealing in subtle ways, the subjective nature of time.  Each of these works suggest questions related to the nature of illusive experience and how or if it can be captured, bringing inevitable connections to authorship, loss, memory and memento mori

David Bowen
tele-present wind
Image
Biography
Credits

Spencer Finch (USA)
2 hours, 2 minutes, 2 seconds (Wind at Walden Pond, March 12, 2007)
Image
Biography
Credits

Nathalie Miebach (USA)
Hurricane Noel III
Image
Biography
Credits

Chris Welsby (UK)
Wind Vane
Image
Biography
Credits

Hours
10:00am – 5:00pm Tuesday – Sunday
10:00am – 8:00pm Thursdays
Closed Monday

Address
New Media Gallery
3rd Floor Anvil Centre
777 Columbia Street
New Westminster, BC V3M 1B6

If you want to see the images and biographies for the artists participating in ‘winds’, please go here..

So there you have it, science events and an exhibition in the Vancouver* area for July 2019.

*July 23, 2019 Correction: The word ‘and’ was removed from the final sentence for grammatical correctness.

**July 23, 2019 Correction: I changed the word ‘cure’ to ‘treatment’ so as to be more accurate. The word ‘cure’ suggests permanence and Glybera is supposed to be effective for 10 years or longer but no one really knows.

***Added the word ‘be’ for grammatical correctness on Nov. 30, 2020.

Brainy and brainy: a novel synaptic architecture and a neuromorphic computing platform called SpiNNaker

Leave a reply

I have two items about brainlike computing. The first item hearkens back to memristors, a topic I have been following since 2008. (If you’re curious about the various twists and turns just enter  the term ‘memristor’ in this blog’s search engine.) The latest on memristors is from a team than includes IBM (US), École Politechnique Fédérale de Lausanne (EPFL; Swizterland), and the New Jersey Institute of Technology (NJIT; US). The second bit comes from a Jülich Research Centre team in Germany and concerns an approach to brain-like computing that does not include memristors.

Multi-memristive synapses

In the inexorable march to make computers function more like human brains (neuromorphic engineering/computing), an international team has announced its latest results in a July 10, 2018 news item on Nanowerk,

Two New Jersey Institute of Technology (NJIT) researchers, working with collaborators from the IBM Research Zurich Laboratory and the École Polytechnique Fédérale de Lausanne, have demonstrated a novel synaptic architecture that could lead to a new class of information processing systems inspired by the brain.

The findings are an important step toward building more energy-efficient computing systems that also are capable of learning and adaptation in the real world. …

A July 10, 2018 NJIT news release (also on EurekAlert) by Tracey Regan, which originated by the news item, adds more details,

The researchers, Bipin Rajendran, an associate professor of electrical and computer engineering, and S. R. Nandakumar, a graduate student in electrical engineering, have been developing brain-inspired computing systems that could be used for a wide range of big data applications.

Over the past few years, deep learning algorithms have proven to be highly successful in solving complex cognitive tasks such as controlling self-driving cars and language understanding. At the heart of these algorithms are artificial neural networks – mathematical models of the neurons and synapses of the brain – that are fed huge amounts of data so that the synaptic strengths are autonomously adjusted to learn the intrinsic features and hidden correlations in these data streams.

However, the implementation of these brain-inspired algorithms on conventional computers is highly inefficient, consuming huge amounts of power and time. This has prompted engineers to search for new materials and devices to build special-purpose computers that can incorporate the algorithms. Nanoscale memristive devices, electrical components whose conductivity depends approximately on prior signaling activity, can be used to represent the synaptic strength between the neurons in artificial neural networks.

While memristive devices could potentially lead to faster and more power-efficient computing systems, they are also plagued by several reliability issues that are common to nanoscale devices. Their efficiency stems from their ability to be programmed in an analog manner to store multiple bits of information; however, their electrical conductivities vary in a non-deterministic and non-linear fashion.

In the experiment, the team showed how multiple nanoscale memristive devices exhibiting these characteristics could nonetheless be configured to efficiently implement artificial intelligence algorithms such as deep learning. Prototype chips from IBM containing more than one million nanoscale phase-change memristive devices were used to implement a neural network for the detection of hidden patterns and correlations in time-varying signals.

“In this work, we proposed and experimentally demonstrated a scheme to obtain high learning efficiencies with nanoscale memristive devices for implementing learning algorithms,” Nandakumar says. “The central idea in our demonstration was to use several memristive devices in parallel to represent the strength of a synapse of a neural network, but only chose one of them to be updated at each step based on the neuronal activity.”

Here’s a link to and a citation for the paper,

Neuromorphic computing with multi-memristive synapses by Irem Boybat, Manuel Le Gallo, S. R. Nandakumar, Timoleon Moraitis, Thomas Parnell, Tomas Tuma, Bipin Rajendran, Yusuf Leblebici, Abu Sebastian, & Evangelos Eleftheriou. Nature Communications volume 9, Article number: 2514 (2018) DOI: https://doi.org/10.1038/s41467-018-04933-y Published 28 June 2018

This is an open access paper.

Also they’ve got a couple of very nice introductory paragraphs which I’m including here, (from the June 28, 2018 paper in Nature Communications; Note: Links have been removed),

The human brain with less than 20 W of power consumption offers a processing capability that exceeds the petaflops mark, and thus outperforms state-of-the-art supercomputers by several orders of magnitude in terms of energy efficiency and volume. Building ultra-low-power cognitive computing systems inspired by the operating principles of the brain is a promising avenue towards achieving such efficiency. Recently, deep learning has revolutionized the field of machine learning by providing human-like performance in areas, such as computer vision, speech recognition, and complex strategic games1. However, current hardware implementations of deep neural networks are still far from competing with biological neural systems in terms of real-time information-processing capabilities with comparable energy consumption.

One of the reasons for this inefficiency is that most neural networks are implemented on computing systems based on the conventional von Neumann architecture with separate memory and processing units. There are a few attempts to build custom neuromorphic hardware that is optimized to implement neural algorithms2,3,4,5. However, as these custom systems are typically based on conventional silicon complementary metal oxide semiconductor (CMOS) circuitry, the area efficiency of such hardware implementations will remain relatively low, especially if in situ learning and non-volatile synaptic behavior have to be incorporated. Recently, a new class of nanoscale devices has shown promise for realizing the synaptic dynamics in a compact and power-efficient manner. These memristive devices store information in their resistance/conductance states and exhibit conductivity modulation based on the programming history6,7,8,9. The central idea in building cognitive hardware based on memristive devices is to store the synaptic weights as their conductance states and to perform the associated computational tasks in place.

The two essential synaptic attributes that need to be emulated by memristive devices are the synaptic efficacy and plasticity. …

It gets more complicated from there.

Now onto the next bit.

SpiNNaker

At a guess, those capitalized N’s are meant to indicate ‘neural networks’. As best I can determine, SpiNNaker is not based on the memristor. Moving on, a July 11, 2018 news item on phys.org announces work from a team examining how neuromorphic hardware and neuromorphic software work together,

A computer built to mimic the brain’s neural networks produces similar results to that of the best brain-simulation supercomputer software currently used for neural-signaling research, finds a new study published in the open-access journal Frontiers in Neuroscience. Tested for accuracy, speed and energy efficiency, this custom-built computer named SpiNNaker, has the potential to overcome the speed and power consumption problems of conventional supercomputers. The aim is to advance our knowledge of neural processing in the brain, to include learning and disorders such as epilepsy and Alzheimer’s disease.

A July 11, 2018 Frontiers Publishing news release on EurekAlert, which originated the news item, expands on the latest work,

“SpiNNaker can support detailed biological models of the cortex–the outer layer of the brain that receives and processes information from the senses–delivering results very similar to those from an equivalent supercomputer software simulation,” says Dr. Sacha van Albada, lead author of this study and leader of the Theoretical Neuroanatomy group at the Jülich Research Centre, Germany. “The ability to run large-scale detailed neural networks quickly and at low power consumption will advance robotics research and facilitate studies on learning and brain disorders.”

The human brain is extremely complex, comprising 100 billion interconnected brain cells. We understand how individual neurons and their components behave and communicate with each other and on the larger scale, which areas of the brain are used for sensory perception, action and cognition. However, we know less about the translation of neural activity into behavior, such as turning thought into muscle movement.

Supercomputer software has helped by simulating the exchange of signals between neurons, but even the best software run on the fastest supercomputers to date can only simulate 1% of the human brain.

“It is presently unclear which computer architecture is best suited to study whole-brain networks efficiently. The European Human Brain Project and Jülich Research Centre have performed extensive research to identify the best strategy for this highly complex problem. Today’s supercomputers require several minutes to simulate one second of real time, so studies on processes like learning, which take hours and days in real time are currently out of reach.” explains Professor Markus Diesmann, co-author, head of the Computational and Systems Neuroscience department at the Jülich Research Centre.

He continues, “There is a huge gap between the energy consumption of the brain and today’s supercomputers. Neuromorphic (brain-inspired) computing allows us to investigate how close we can get to the energy efficiency of the brain using electronics.”

Developed over the past 15 years and based on the structure and function of the human brain, SpiNNaker — part of the Neuromorphic Computing Platform of the Human Brain Project — is a custom-built computer composed of half a million of simple computing elements controlled by its own software. The researchers compared the accuracy, speed and energy efficiency of SpiNNaker with that of NEST–a specialist supercomputer software currently in use for brain neuron-signaling research.

“The simulations run on NEST and SpiNNaker showed very similar results,” reports Steve Furber, co-author and Professor of Computer Engineering at the University of Manchester, UK. “This is the first time such a detailed simulation of the cortex has been run on SpiNNaker, or on any neuromorphic platform. SpiNNaker comprises 600 circuit boards incorporating over 500,000 small processors in total. The simulation described in this study used just six boards–1% of the total capability of the machine. The findings from our research will improve the software to reduce this to a single board.”

Van Albada shares her future aspirations for SpiNNaker, “We hope for increasingly large real-time simulations with these neuromorphic computing systems. In the Human Brain Project, we already work with neuroroboticists who hope to use them for robotic control.”

Before getting to the link and citation for the paper, here’s a description of SpiNNaker’s hardware from the ‘Spiking neural netowrk’ Wikipedia entry, Note: Links have been removed,

Neurogrid, built at Stanford University, is a board that can simulate spiking neural networks directly in hardware. SpiNNaker (Spiking Neural Network Architecture) [emphasis mine], designed at the University of Manchester, uses ARM processors as the building blocks of a massively parallel computing platform based on a six-layer thalamocortical model.[5]

Now for the link and citation,

Performance Comparison of the Digital Neuromorphic Hardware SpiNNaker and the Neural Network Simulation Software NEST for a Full-Scale Cortical Microcircuit Model by
Sacha J. van Albada, Andrew G. Rowley, Johanna Senk, Michael Hopkins, Maximilian Schmidt, Alan B. Stokes, David R. Lester, Markus Diesmann, and Steve B. Furber. Neurosci. 12:291. doi: 10.3389/fnins.2018.00291 Published: 23 May 2018

As noted earlier, this is an open access paper.

Hallucinogenic molecules and the brain

Leave a reply

Psychedelic drugs seems to be enjoying a ‘moment’. After decades of being vilified and  declared illegal (in many jurisdictions), psychedelic (or hallucinogenic) drugs are once again being tested for use in therapy. A Sept. 1, 2017 article by Diana Kwon for The Scientist describes some of the latest research (I’ve excerpted the section on molecules; Note: Links have been removed),

Mind-bending molecules

© SEAN MCCABE

All the classic psychedelic drugs—psilocybin, LSD, and N,N-dimethyltryptamine (DMT), the active component in ayahuasca—activate serotonin 2A (5-HT2A) receptors, which are distributed throughout the brain. In all likelihood, this receptor plays a key role in the drugs’ effects. Krähenmann [Rainer Krähenmann, a psychiatrist and researcher at the University of Zurich]] and his colleagues in Zurich have discovered that ketanserin, a 5-HT2A receptor antagonist, blocks LSD’s hallucinogenic properties and prevents individuals from entering a dreamlike state or attributing personal relevance to the experience.12,13

Other research groups have found that, in rodent brains, 2,5-dimethoxy-4-iodoamphetamine (DOI), a highly potent and selective 5-HT2A receptor agonist, can modify the expression of brain-derived neurotrophic factor (BDNF)—a protein that, among other things, regulates neuronal survival, differentiation, and synaptic plasticity. This has led some scientists to hypothesize that, through this pathway, psychedelics may enhance neuroplasticity, the ability to form new neuronal connections in the brain.14 “We’re still working on that and trying to figure out what is so special about the receptor and where it is involved,” says Katrin Preller, a postdoc studying psychedelics at the University of Zurich. “But it seems like this combination of serotonin 2A receptors and BDNF leads to a kind of different organizational state in the brain that leads to what people experience under the influence of psychedelics.”

This serotonin receptor isn’t limited to the central nervous system. Work by Charles Nichols, a pharmacology professor at Louisiana State University, has revealed that 5-HT2A receptor agonists can reduce inflammation throughout the body. Nichols and his former postdoc Bangning Yu stumbled upon this discovery by accident, while testing the effects of DOI on smooth muscle cells from rat aortas. When they added this drug to the rodent cells in culture, it blocked the effects of tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine.

“It was completely unexpected,” Nichols recalls. The effects were so bewildering, he says, that they repeated the experiment twice to convince themselves that the results were correct. Before publishing the findings in 2008,15 they tested a few other 5-HT2A receptor agonists, including LSD, and found consistent anti-inflammatory effects, though none of the drugs’ effects were as strong as DOI’s. “Most of the psychedelics I have tested are about as potent as a corticosteroid at their target, but there’s something very unique about DOI that makes it much more potent,” Nichols says. “That’s one of the mysteries I’m trying to solve.”

After seeing the effect these drugs could have in cells, Nichols and his team moved on to whole animals. When they treated mouse models of system-wide inflammation with DOI, they found potent anti-inflammatory effects throughout the rodents’ bodies, with the strongest effects in the small intestine and a section of the main cardiac artery known as the aortic arch.16 “I think that’s really when it felt that we were onto something big, when we saw it in the whole animal,” Nichols says.

The group is now focused on testing DOI as a potential therapeutic for inflammatory diseases. In a 2015 study, they reported that DOI could block the development of asthma in a mouse model of the condition,17 and last December, the team received a patent to use DOI for four indications: asthma, Crohn’s disease, rheumatoid arthritis, and irritable bowel syndrome. They are now working to move the treatment into clinical trials. The benefit of using DOI for these conditions, Nichols says, is that because of its potency, only small amounts will be required—far below the amounts required to produce hallucinogenic effects.

In addition to opening the door to a new class of diseases that could benefit from psychedelics-inspired therapy, Nichols’s work suggests “that there may be some enduring changes that are mediated through anti-inflammatory effects,” Griffiths [Roland Griffiths, a psychiatry professor at Johns Hopkins University] says. Recent studies suggest that inflammation may play a role in a number of psychological disorders, including depression18 and addiction.19

“If somebody has neuroinflammation and that’s causing depression, and something like psilocybin makes it better through the subjective experience but the brain is still inflamed, it’s going to fall back into the depressed rut,” Nichols says. But if psilocybin is also treating the inflammation, he adds, “it won’t have that rut to fall back into.”

…

If it turns out that psychedelics do have anti-inflammatory effects in the brain, the drugs’ therapeutic uses could be even broader than scientists now envision. “In terms of neurodegenerative disease, every one of these disorders is mediated by inflammatory cytokines,” says Juan Sanchez-Ramos, a neuroscientist at the University of South Florida who in 2013 reported that small doses of psilocybin could promote neurogenesis in the mouse hippocampus.20 “That’s why I think, with Alzheimer’s, for example, if you attenuate the inflammation, it could help slow the progression of the disease.”

For anyone who was never exposed to the anti-hallucinogenic drug campaigns, this turn of events is mindboggling. There was a great deal of concern especially with LSD in the 1960s and it was not entirely unfounded. In my own family, a distant cousin, while under the influence of the drug, jumped off a building believing he could fly.  So, Kwon’s story opening with a story about someone being treated successfully for depression with a psychedelic drug was surprising to me . Why these drugs are being used successfully for psychiatric conditions when so much damage was apparently done under the influence in decades past may have something to do with taking the drugs in a controlled environment and, possibly, smaller dosages.