AFM and SEM images of graphene oxide and the behavioral model of short- and long-term fear memories induced by aversive olfactory stimulus.
AFM and SEM images of graphene oxide and the behavioral model of short- and long-term fear memories induced by aversive olfactory stimulus.

Tiny flakes of graphene oxide (GO) affect the response of synapses in the brain, according to researchers from the International School for Advanced Studies (SISSA) in Italy, Catalan Institute of Nanoscience and Nanotechnology (ICN2) in Spain, Ribeirao Preto Medical School of the University of Sao Paulo in Brazil, and The University of Manchester in the UK [Biagioni et al., Biomaterials 271 (2021) 120749,].

Synapses in the central nervous system (CNS) relay signals among neurons. Changes in synapse, which are known as ‘synaptic plasticity’, are crucial to learning and the laying down new memories. But in the amygdala complex, this phenomenon is implicated in anxiety and disorders like dementia. When under stress, neurons in part of the brain respond in a ‘hyper’ excited manner, leading to adverse memories or post-traumatic stress disorder (PTSD). Now researchers led by Laura Ballerini at SISSA, along with other partners in the European Graphene Flagship project, have  found that GO interferes with this process.

“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,” explains Ballerini.

The researchers used a model of PTSD where rats are exposed to the scent of a predator, a cat, and respond with a typical fright response.

“Exposure to a predator can modify neuronal connections - a phenomenon known as plasticity - and increases synaptic activity in a specific area of the amygdala,” explains first author of the study, Audrey Franceschi Biagioni. “If exposed to a predator odor, the rat has a defensive response, holing up, [which] is so well-imprinted in the memory that the animal remembers the odor of the predator and acts out the same protective behavior.”

Remarkably, the researchers found that rats sensitized to the scent of a cat ‘forgot’ their fear response after injection with GO directly into the amygdala part of the brain. The researchers think that GO temporarily interferes with synaptic plasticity, impairing the formation of long-term adverse memories in response to a threat and reducing anxiety-related behaviors. Administration of GO could provide a means of preventing unwanted synaptic plasticity, blocking the reinforcement of unpleasant memories, which could be particularly useful in the treatment of PTSD.

“Our experiments are a proof-of-concept of the potential use of graphene oxides nanoflakes as a therapeutic for the nervous system. However, many challenges have to be addressed before having graphene in the clinic,” points out Ballerini.

Any potential toxic effect of GO would have to be ruled out and less invasive delivery methods would need to be developed. In the meantime, Ballerini and her colleagues are investigating if GO interferes with other forms of pathological synaptic plasticity.