Graphene nanoparticles inhibit the development of stress-related behaviors in the spine

New research shows that the nanomaterial acts on the excitatory synapses, influencing the development of stress-related behaviors in the spine.

Efficient, unique, with adjustable and harmless action: the identity of the perfect biomaterial seems to match graphene flakes, the subject of a new study conducted by SISSA – Trieste International School for Advanced Studies, Catalan Institute of Nano-science and Nanotechnology (ICN2) of Barcelona and the National Graphene Institute of the University of Manchester, in the framework of the Swedish European project Graphene.

This nanomaterial has shown that it is possible to interact with the functions of the nervous system in the spine in a very specific way, inhibiting the construction of a pathology process that leads to anxiety-related behavior.

“We have previously shown that when graphene flakes are delivered to neurons they independently engage excitatory synapses by inhibiting transient inhibition of glutamate release from presynaptic centers” said Laura Ballerini of SISSA, director the team that conducted the research study ‘Graphene oxide inhibits lateral amygdala synaptic dysfunctional plasticity and reverses long-term anxiety behavior in rats’, recently published in Biomaterials, co-authored by Audrey Franceschi Biagioni, Giada Cellot, Elisa Pati, Neus Lozano, Belén Ballesteros, Raffaele Casani, Norberto Cysne Coimbra, Kostas Kostarelos.

“We examined whether such a decrease in synaptic activity was sufficient to alter associated behaviors, especially those of pathological ones that develop due to transient and local hyperactivation of excitatory synapses”.

This approach would strengthen the strategy for selective and noninvasive targeting of synapses to prevent the development of brain pathologies by using the so-called precision therapies.

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

“We analyzed the immune behavior induced by rats with the presence of a predator, using the exposure to cat odor, to induce disturbing memory” explained Audrey Franceschi Biagioni of SISSA, the first author of the study.

“If exposed to the smell of the predator, the rat has a protective response, healing, and this experience is so well remembered, when the animal is placed in the same context even six days later. that is, the animal remembers the smell of the predator and acts the same protective behavior. This is a well-known and confirmed model, which we would use for weight bearing.

Exposure to the predator can alter neuronal connections – a phenomenon known technically plasticity – and increase synaptic activity in a specific area of ​​the amygdala that thus represented the target of our study to determine the effect of the nanomaterials ”.

Laura Ballerini said: “We suggested that graphene flakes we have shown to block excitatory synapses for a short time (without causing inflammation, damage to neurons or other side effects) could be injected into the late amygdala. when the plasticity associated with memory was confirmed.

If the nanomaterial was effective in inhibiting excitatory synapses, it should inhibit plasticity and reduce the anxiety-related response. And here ‘s what happened: the animals presented with graphene flakes forgot, after six days, “the anxiety – related responses, rescuing their behavior”.

The second part of the research was conducted in vitro.

In vivo we could only observe behavioral changes and could not evaluate the effect of graphene flakes on synapses. In vitro experiments allowed us to work on a simpler model, to gain insight into the mechanisms by which the graphene flakes can interact with neurons. “

Giada Cellot, First Author and Researcher Study, Scuola Internazionale Superiore di Studi Avanzati

We used neuronal cultures derived from the amygdala, the region of the brain where the stress response occurs, and found that nanomaterials had specific effects for the excitatory synapses and brief exposure to graphene flakes could prevent pathological plasticity of the synapses ”.

Thanks to these findings, graphene flakes have been shown to have the potential as nanotools (biochemical devices made up of nanomaterials) that can act in a specific way and restore synaptic activity. to prevent pathology process and thus could also be used to transport drugs or for other applications in the field of precision medicine.