Tag Archives: Neus Lozano

Impact of graphene flakes (nanoparticles) on neurons

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This research suggests that graphene flakes might have an impact on anxiety-related behaviour. If I read the work correctly, the graphene flakes don’t exacerbate anxiety but, instead, may provide relief.

A March 10, 2021 news item on phys.org announces the research into graphene flakes and neurons (rat), Note: Links have been removed,

Effective, specific, with a reversible and non-harmful action: the identikit of the perfect biomaterial seems to correspond to graphene flakes, the subject of a new study carried out by SISSA—International School for Advanced Studies of Trieste, Catalan Institute of Nanoscience and Nanotechnology (ICN2) of Barcelona, and the National Graphene Institute of the University of Manchester, as part of the European Graphene Flagship project. This nanomaterial has demonstrated the ability to interact with the functions of the nervous system in vertebrates in a very specific manner, interrupting the building up of a pathological process that leads to anxiety-related behavior.

“We previously showed that when graphene flakes are delivered to neurons they interfere spontaneously with excitatory synapses by transiently preventing glutamate release from presynaptic terminals,” says Laura Ballerini of SISSA, the leader of the team that carried out the research study “Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats,” recently published in Biomaterials.

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A March 10, 2021 Scuola Internazionale Superiore di Studi Avanzati (SISSA) press release (also on EurekAlert), which originated the news item, provides more detail,

“We investigated whether such a reduction in synaptic activity was sufficient to modify related behaviours, in particular the pathological ones that develop due to a transient and localised hyper-function of excitatory synapses”. This approach would fortify the strategy of selective and transient targeting of synapses to prevent the development of brain pathologies by using the so-called precise medicine treatments.

To test this hypothesis, the team focused on post-traumatic stress disorder (PTSD) and carried out the experiments in two phases, in vivo and in vitro.

“We analysed defensive behaviours caused in rats [emphasis mine] by the presence of a predator, using the exposure to cat odour, to induce an aversive memory” explains Audrey Franceschi Biagioni of SISSA, the first author of the study. “If exposed to the predator odour, the rat has a defensive response, holing up, and this experience is so well-imprinted in the memory, that when the animal is placed in the same context even six days later, the animal remembers the odour of the predator and acts the same protective behaviour. This is a well-known and consolidated model, that we used to reproduce a stress behaviour. Exposure to the predator can modify neuronal connections – a phenomenon that is technically known as plasticity – and increases synaptic activity in a specific area of the amygdala that therefore represented the target of our study to test the effects of the nanomaterial”.

Laura Ballerini adds: “We hypothesised that graphene flakes that we showed to temporarily inhibit excitatory synapses (without causing inflammation, damage to neurons or other side effects) could be injected in the lateral amygdala when the plasticity associated with memory was consolidated. If the nanomaterial was efficient in blocking excitatory synapses, it should inhibit plasticity and decrease the anxiety related response. And this is what happened: the animals that were administered with graphene flakes, after six days, “forgot” the anxiety related responses, rescuing their behaviour”.

The second part of the research was performed in vitro. “In vivo we could observe only behavioural changes and could not evaluate the impact of the graphene flakes on synapses,” explains Giada Cellot, researcher at SISSA and first author of the study together with Audrey Franceschi Biagioni. “In vitro experiments allowed to work on a simplified model, to get insight about the mechanisms through which the graphene flakes can interact with neurons. We used neuronal cultures obtained from the amygdala, the region of the brain where the stress response occurs, and we observed that the effects of nanomaterials were specific for the excitatory synapses and a short exposure to graphene flakes could prevent the pathological plasticity of the synapses”.

Thanks to these findings, graphene flakes have shown their potential as nanotools (biomedical tools composed of nanomaterials) that could act in a specific and reversible way on synaptic activity to interrupt a pathological process and therefore they might be used also to transport drugs or for other applications in the field of precision medicine.

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

Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats by Audrey Franceschi Biagionia1, Giada Cellot, Elisa Pati, Neus Lozano, Belén Ballesteros, Raffaele Casani, Norberto Cysne Coimbra, Kostas Kostarelos, Laura Ballerini. Biomaterials Volume 271, April 2021, 120749 DOI: https://doi.org/10.1016/j.biomaterials.2021.120749

This paper is open access.

Calming a synapse (part of a neuron) with graphene flakes

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As we continue to colonize our own brains, there’s more news of graphene and neurons (see my Feb. 1, 2016 post featuring research from the same team in Italy featured in this post). A May 10, 2016 news item on ScienceDaily highlights work that could be used for epilepsy,

Innovative graphene technology to buffer the activity of synapses– this is the idea behind a recently-published study in the journal ACS Nano coordinated by the International School for Advanced Studies in Trieste (SISSA) and the University of Trieste. In particular, the study showed how effective graphene oxide flakes are at interfering with excitatory synapses, an effect that could prove useful in new treatments for diseases like epilepsy.

I guess the press release took a while to make its way through translation, here’s more from the April 10, 2016 SISSA (International School for Advanced Studies) press release (also on EurekAlert),

The laboratory of SISSA’s Laura Ballerini in collaboration with the University of Trieste, the University of Manchester and the University of Castilla -la Mancha, has discovered a new approach to modulating synapses. This methodology could be useful for treating diseases in which electrical nerve activity is altered. Ballerini and Maurizio Prato (University of Trieste) are the principal investigators of the project within the European flagship on graphene, a far-reaching 10-year international collaboration (one billion euros in funding) that studies innovative uses of the material.

Traditional treatments for neurological diseases generally include drugs that act on the brain or neurosurgery. Today however, graphene technology is showing promise for these types of applications, and is receiving increased attention from the scientific community. The method studied by Ballerini and colleagues uses “graphene nano-ribbons” (flakes) which buffer activity of synapses simply by being present.

“We administered aqueous solutions of graphene flakes to cultured neurons in ‘chronic’ exposure conditions, repeating the operation every day for a week. Analyzing functional neuronal electrical activity, we then traced the effect on synapses” says Rossana Rauti, SISSA researcher and first author of the study.

In the experiments, size of the flakes varied (10 microns or 80 nanometers) as well as the type of graphene: in one condition graphene was used, in another, graphene oxide. “The ‘buffering’ effect on synaptic activity happens only with smaller flakes of graphene oxide and not in other conditions,” says Ballerini. “The effect, in the system we tested, is selective for the excitatory synapses, while it is absent in inhibitory ones”

A Matter of Size

What is the origin of this selectivity? “We know that in principle graphene does not interact chemically with synapses in a significant way- its effect is likely due to the mere presence of synapses,” explains SISSA researcher and one of the study’s authors, Denis Scaini. “We do not yet have direct evidence, but our hypothesis is that there is a link with the sub-cellular organization of the synaptic space.”

A synapse is a contact point between one neuron and another where the nervous electrical signal “jumps” between a pre and post-synaptic unit. [emphasis mine] There is a small gap or discontinuity where the electrical signal is “translated” by a neurotransmitter and released by pre-synaptic termination into the extracellular space and reabsorbed by the postsynaptic space, to be translated again into an electrical signal. The access to this space varies depending on the type of synapses: “For the excitatory synapses, the structure’s organization allows higher exposure for the graphene flakes interaction, unlike inhibitory synapses, which are less physically accessible in this experimental model,” says Scaini.

Another clue that distance and size could be crucial in the process is found in the observation that graphene performs its function only in the oxidized form. “Normal graphene looks like a stretched and stiff sheet while graphene oxide appears crumpled, and thus possibly favoring interface with the synaptic space, ” adds Rauti.

Administering graphene flake solutions leaves the neurons alive and intact. For this reason the team thinks they could be used in biomedical applications for treating certain diseases. “We may imagine to target a drug by exploiting the apparent flakes’ selectivity for synapses, thus targeting directly the basic functional unit of neurons”concludes Ballerini.

That’s a nice description of neurons, synapses, and neurotransmitters.

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

Graphene Oxide Nanosheets Reshape Synaptic Function in Cultured Brain Networks by Rossana Rauti, Neus Lozano, Veronica León, Denis Scaini†, Mattia Musto, Ilaria Rago, Francesco P. Ulloa Severino, Alessandra Fabbro, Loredana Casalis, Ester Vázquez, Kostas Kostarelos, Maurizio Prato, and Laura Ballerini. ACS Nano, 2016, 10 (4), pp 4459–4471
DOI: 10.1021/acsnano.6b00130 Publication Date (Web): March 31, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.