Tag Archives: neurotransmitter

Bioelectronics: creating components that speak the body’s own language

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This is work is still in its early stages but the idea that the body could be stimulated to release more of its own pain relievers is exciting. From a Nov. 2, 2016 news item on ScienceDaily,

With a microfabricated ion pump built from organic electronic components, ions can be sent to nerve or muscle cells at the speed of the nervous system and with a precision of a single cell. “Now we can start to develop components that speak the body’s own language,” says Daniel Simon, head of bioelectronics research at the Laboratory of Organic Electronics, Linköping University, Campus Norrköping.

A Nov. 2, 2016 Linköping University press release (also on EurekAlert), which originated the news item, discusses the research in more detail,

Our nerve and muscle cells send signals to each other using ions and molecules. Certain substances, such as the neurotransmitter GABA (gamma aminobutyric acid), are important signal substances throughout the central nervous system. Eighteen months ago, researchers at the Laboratory of Organic Electronics demonstrated an ion pump which researchers at the Karolinska Institutet could use to reduce the sensation of pain in awake, freely-moving rats. The ion pump delivered GABA directly to the rat´s spinal cord. The news that researchers could deliver the body’s own neurotransmitters was published in Science Advances and garnered intense interest all over the world.

The research group at the Laboratory of Organic Electronics has now achieved another major advance and developed a significantly smaller and more rapid ion pump that transmits signals nearly as rapidly as the cells themselves, and with a precision on the scale of an individual cell. …

“Our skilled doctoral students, Amanda Jonsson and Theresia Arbring Sjöström, have succeeded with the last important part of the puzzle in the development of the ion pump. When a signal passes between two synapses it takes 1-10 milliseconds, and we are now very close to the nervous system’s own speed,” says Magnus Berggren, professor of organic electronics and director of the Laboratory of Organic Electronics.

“We conclude that we have produced artificial nerves that can communicate seamlessly with the nervous system. After more than 10 years’ research we have finally got all the parts of the puzzle in place,” he says.

Amanda Jonsson, who together with Theresia Arbring Sjöström is principal author of the article in Science Advances, has developed the pain-alleviating ion pump as part of her doctoral studies. She proudly presents a glass disk with many of the new miniaturized ion pumps. Some pumps have only a single outlet, but others have six tiny point outlets.

“We can make them with several outlets, it’s just as easy as making one. And all of the outlets can be individually controlled. Previously we could only transport ions horizontally and from all outputs at the same time. Now, however, we can deliver the ions vertically, which makes the distance they have to be transported as short as a micrometre,” she explains.

All of the outputs of the ion pump can also be rapidly switched on or off with the aid of micrometre-sized ion diodes.

“The ions are released rapidly by an electrical signal, in the same way that the neurotransmitter is released in a synapse,” says Theresia Arbring Sjöström.

Organic electronic components have a major advantage here: they can conduct both ions and electricity. In this case, the material PEDOT:PSS enables the electrical signals to be converted to chemical signals that the body understands.

The ion diode has recently been developed, as has the material that forms the basis of the new rapid ion pump.

“The new material makes it possible to build with a precision and reliability not possible in previous versions of the ion pump,” says Daniel Simon.

The new ion pump has so far only been tested in the laboratory. The next step will be to test it with live cells and the researchers hope eventually to, for example alleviate pain, stop epileptic seizures, and reduce the symptoms of Parkinsons disease, using exactly the required dose at exactly the affected cells. Communication using the cell´s own language, and the cell´s own speed.

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

Chemical delivery array with millisecond neurotransmitter release by Amanda Jonsson, Theresia Arbring Sjöström, Klas Tybrandt, Magnus Berggren, and Daniel T. Simon. Science Advances  02 Nov 2016: Vol. 2, no. 11, e1601340 DOI: 10.1126/sciadv.1601340

This paper is open access.

Titanium dioxide nanoparticles and the brain

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This research into titanium dioxide nanoparticles and possible effects on your brain should they pass the blood-brain barrier comes from the University of Nebraska-Lincoln (US) according to a Dec. 15, 2015 news item on Nanowerk (Note: A link has been removed),

Even moderate concentrations of a nanoparticle used to whiten certain foods, milk and toothpaste could potentially compromise the brain’s most numerous cells, according to a new study from the University of Nebraska-Lincoln (Nanoscale, “Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles”).

A Dec. 14, 2015 University of Nebraska-Lincoln news release, which originated the news item, provides more detail (Note: Links have been removed),

The researchers examined how three types of titanium dioxide nanoparticles [rutile, anatase, and commercially available P25 TiO2 nanoparticles], the world’s second-most abundant nanomaterial, affected the functioning of astrocyte cells. Astrocytes help regulate the exchange of signal-carrying neurotransmitters in the brain while also supplying energy to the neurons that process those signals, among many other functions.

The team exposed rat-derived astrocyte cells to nanoparticle concentrations well below the extreme levels that have been shown to kill brain cells but are rarely encountered by humans. At the study’s highest concentration of 100 parts per million, or PPM, two of the nanoparticle types still killed nearly two-thirds of the astrocytes within a day. That mortality rate fell to between half and one-third of cells at 50 PPM, settling to about one-quarter at 25 PPM.

Yet the researchers found evidence that even surviving cells are severely impaired by exposure to titanium dioxide nanoparticles. Astrocytes normally take in and process a neurotransmitter called glutamate that plays wide-ranging roles in cognition, memory and learning, along with the formation, migration and maintenance of other cells.

When allowed to accumulate outside cells, however, glutamate becomes a potent toxin that kills neurons and may increase the risk of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The study reported that one of the nanoparticle types reduced the astrocytes’ uptake of glutamate by 31 percent at concentrations of just 25 PPM. Another type decreased that uptake by 45 percent at 50 PPM.

The team further discovered that the nanoparticles upset the intricate balance of protein dynamics occurring within astrocytes’ mitochondria, the cellular organelles that help regulate energy production and contribute to signaling among cells. Titanium dioxide exposure also led to other signs of mitochondrial distress, breaking apart a significant proportion of the mitochondrial network at 100 PPM.

“These events are oftentimes predecessors of cell death,” said Oleh Khalimonchuk, a UNL assistant professor of biochemistry who co-authored the study. “Usually, people are looking at those ultimate consequences, but what happens before matters just as much. Those little damages add up over time. Ultimately, they’re going to cause a major problem.”

Khalimonchuk and fellow author Srivatsan Kidambi, assistant professor of chemical and biomolecular engineering, cautioned that more research is needed to determine whether titanium dioxide nanoparticles can avoid digestion and cross the blood-brain barrier that blocks the passage of many substances. [emphasis mine]

However, the researchers cited previous studies that have discovered these nanoparticles in the brain tissue of animals with similar blood-brain barriers. [emphasis mine] The concentrations of nanoparticles found in those specimens served as a reference point for the levels examined in the new study.

“There’s evidence building up now that some of these particles can actually cross the (blood-brain) barrier,” Khalimonchuk said. “Few molecules seem to be able to do so, but it turns out that there are certain sites in the brain where you can get this exposure.”

Kidambi said the team hopes the study will help facilitate further research on the presence of nanoparticles in consumer and industrial products.

“We’re hoping that this study will get some discussion going, because these nanoparticles have not been regulated,” said Kidambi, who also holds a courtesy appointment with the University of Nebraska Medical Center. “If you think about anything white – milk, chewing gum, toothpaste, powdered sugar – all these have nanoparticles in them.

“We’ve found that some nanoparticles are safe and some are not, so we are not saying that all of them are bad. Our reasoning is that … we need to have a classification of ‘safe’ versus ‘not safe,’ along with concentration thresholds (for each type). It’s about figuring out how the different forms affect the biology of cells.

I notice the researchers are being careful about alarming anyone unduly while emphasizing the importance of this research. For anyone curious enough to read the paper, here’s a link to and a citation for it,

Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles by Christina L. Wilson, Vaishaali Natarajan, Stephen L. Hayward, Oleh Khalimonchuk and   Srivatsan Kidambi. Nanoscale, 2015,7, 18477-18488 DOI: 10.1039/C5NR03646A First published online 31 Jul 2015

This is paper is open access although you may need to register on the site.

Final comment, I note this was published online way back in July 2015. Either the paper version of the journal was just published and that’s what’s being promoted or the media people thought they’d try to get some attention for this work by reissuing the publicity. Good on them! It’s hard work getting people to notice things when there is so much information floating around.

Structural color and cephalopods at the University of California Santa Barbara

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I last wrote about structural color in a Feb.7, 2013 posting featuring a marvelous article on the topic by Cristina Luiggi in the The Scientist. As for cephalopods, one of my favourite postings on the topic is a Feb. 1, 2013 posting which features the giant squid, a newly discovered animal of mythical proportions that appears golden in its native habitat in the deep, deep ocean. Happily, there’s a July 25, 2013 news item on Nanowerk which combines structural color and squid,

Color in living organisms can be formed two ways: pigmentation or anatomical structure. Structural colors arise from the physical interaction of light with biological nanostructures. A wide range of organisms possess this ability, but the biological mechanisms underlying the process have been poorly understood.

Two years ago, an interdisciplinary team from UC Santa Barbara [University of California Santa Barbara a.k.a. UCSB] discovered the mechanism by which a neurotransmitter dramatically changes color in the common market squid, Doryteuthis opalescens. That neurotransmitter, acetylcholine, sets in motion a cascade of events that culminate in the addition of phosphate groups to a family of unique proteins called reflectins. This process allows the proteins to condense, driving the animal’s color-changing process.

The July 25, 2013 UC Santa Barbara news release (also on EurekAlert), which originated the news item, provides a good overview of the team’s work to date and the new work occasioning the news release,

Now the researchers have delved deeper to uncover the mechanism responsible for the dramatic changes in color used by such creatures as squids and octopuses. The findings –– published in the Proceedings of the National Academy of Science, in a paper by molecular biology graduate student and lead author Daniel DeMartini and co-authors Daniel V. Krogstad and Daniel E. Morse –– are featured in the current issue of The Scientist.

Structural colors rely exclusively on the density and shape of the material rather than its chemical properties. The latest research from the UCSB team shows that specialized cells in the squid skin called iridocytes contain deep pleats or invaginations of the cell membrane extending deep into the body of the cell. This creates layers or lamellae that operate as a tunable Bragg reflector. Bragg reflectors are named after the British father and son team who more than a century ago discovered how periodic structures reflect light in a very regular and predicable manner.

“We know cephalopods use their tunable iridescence for camouflage so that they can control their transparency or in some cases match the background,” said co-author Daniel E. Morse, Wilcox Professor of Biotechnology in the Department of Molecular, Cellular and Developmental Biology and director of the Marine Biotechnology Center/Marine Science Institute at UCSB.

“They also use it to create confusing patterns that disrupt visual recognition by a predator and to coordinate interactions, especially mating, where they change from one appearance to another,” he added. “Some of the cuttlefish, for example, can go from bright red, which means stay away, to zebra-striped, which is an invitation for mating.”

The researchers created antibodies to bind specifically to the reflectin proteins, which revealed that the reflectins are located exclusively inside the lamellae formed by the folds in the cell membrane. They showed that the cascade of events culminating in the condensation of the reflectins causes the osmotic pressure inside the lamellae to change drastically due to the expulsion of water, which shrinks and dehydrates the lamellae and reduces their thickness and spacing. The movement of water was demonstrated directly using deuterium-labeled heavy water.

When the acetylcholine neurotransmitter is washed away and the cell can recover, the lamellae imbibe water, rehydrating and allowing them to swell to their original thickness. This reversible dehydration and rehydration, shrinking and swelling, changes the thickness and spacing, which, in turn, changes the wavelength of the light that’s reflected, thus “tuning” the color change over the entire visible spectrum.

“This effect of the condensation on the reflectins simultaneously increases the refractive index inside the lamellae,” explained Morse. “Initially, before the proteins are consolidated, the refractive index –– you can think of it as the density –– inside the lamellae and outside, which is really the outside water environment, is the same. There’s no optical difference so there’s no reflection. But when the proteins consolidate, this increases the refractive index so the contrast between the inside and outside suddenly increases, causing the stack of lamellae to become reflective, while at the same time they dehydrate and shrink, which causes color changes. The animal can control the extent to which this happens –– it can pick the color –– and it’s also reversible. The precision of this tuning by regulating the nanoscale dimensions of the lamellae is amazing.”

Another paper by the same team of researchers, published in Journal of the Royal Society Interface, with optical physicist Amitabh Ghoshal as the lead author, conducted a mathematical analysis of the color change and confirmed that the changes in refractive index perfectly correspond to the measurements made with live cells.

A third paper, in press at Journal of Experimental Biology, reports the team’s discovery that female market squid show a set of stripes that can be brightly activated and may function during mating to allow the female to mimic the appearance of the male, thereby reducing the number of mating encounters and aggressive contacts from males. The most significant finding in this study is the discovery of a pair of stripes that switch from being completely transparent to bright white.

“This is the first time that switchable white cells based on the reflectin proteins have been discovered,” Morse noted. “The facts that these cells are switchable by the neurotransmitter acetylcholine, that they contain some of the same reflectin proteins, and that the reflectins are induced to condense to increase the refractive index and trigger the change in reflectance all suggest that they operate by a molecular mechanism fundamentally related to that controlling the tunable color.”

Could these findings one day have practical applications? “In telecommunications we’re moving to more rapid communication carried by light,” said Morse. “We already use optical cables and photonic switches in some of our telecommunications devices. The question is –– and it’s a question at this point –– can we learn from these novel biophotonic mechanisms that have evolved over millions of years of natural selection new approaches to making tunable and switchable photonic materials to more efficiently encode, transmit, and decode information via light?”

In fact, the UCSB researchers are collaborating with Raytheon Vision Systems in Goleta to investigate applications of their discoveries in the development of tunable filters and switchable shutters for infrared cameras. Down the road, there may also be possible applications for synthetic camouflage. [emphasis mine]

There is at least one other research team (the UK’s University of Bristol) considering the camouflage strategies employed cephalopods and, in their case,  zebra fish as noted in my May 4, 2012 posting, Camouflage for everyone.

Getting back to cephalopod in hand, here’s an image from the UC Santa Barbara team,

This shows the diffusion of the neurotransmitter applied to squid skin at upper right, which induces a wave of iridescence traveling to the lower left and progressing from red to blue. Each object in the image is a living cell, 10 microns long; the dark object in the center of each cell is the cell nucleus. [downloaded from http://www.ia.ucsb.edu/pa/display.aspx?pkey=3076]

This shows the diffusion of the neurotransmitter applied to squid skin at upper right, which induces a wave of iridescence traveling to the lower left and progressing from red to blue. Each object in the image is a living cell, 10 microns long; the dark object in the center of each cell is the cell nucleus. [downloaded from http://www.ia.ucsb.edu/pa/display.aspx?pkey=3076]

Fro papers currently available online, here are links and citations,

Optical parameters of the tunable Bragg reflectors in squid by Amitabh Ghoshal, Daniel G. DeMartini, Elizabeth Eck, and Daniel E. Morse. doi: 10.1098/​rsif.2013.0386 J. R. Soc. Interface 6 August 2013 vol. 10 no. 85 20130386

The Royal Society paper is behind a paywall until August 2014.

Membrane invaginations facilitate reversible water flux driving tunable iridescence in a dynamic biophotonic system by Daniel G. DeMartini, Daniel V. Krogstadb, and Daniel E. Morse. Published online before print January 28, 2013, doi: 10.1073/pnas.1217260110
PNAS February 12, 2013 vol. 110 no. 7 2552-2556

The Proceedings of the National Academy of Sciences (PNAS) paper (or the ‘Daniel’ paper as I prefer to think of it)  is behind a paywall.