Researchers from Graphene Flagship partners SISSA in Italy, ICN2 in Spain and the University of Manchester in the UK, in collaboration with the Ribeirão Preto Medical School of the University of São Paulo, have discovered that graphene oxide inhibits anxiety-related behaviours in a model study. They found that injecting graphene oxide into a specific region of the brain silences the neurons responsible for anxious behaviour.

The scientists used a common animal model: just like in the classic cartoon Tom and Jerry, a mouse lives in a hole in the wall of a small room, where it feels protected and safe. Normally, the mouse explores the room freely and without worry. But when the mouse smells a cat, it runs back into its hole, where it knows it is safe. This is a very strong defensive behaviour and the basis for the fight or flight response, which is intrinsic to most animals.

After one week in this environment, the mouse remembers this behaviour, even after the cat’s scent has gone. This is a model for post-traumatic stress disorder (PTSD), a protective anxiety behaviour that arises in response to negative memories. Millions of people around the world suffer from disorders related to PTSD or anxiety.

Laura Ballerini, lead author of the paper and Professor of Physiology at Graphene Flagship partner SISSA, Italy, explains that graphene oxide disables communication between the synapses that cause this type of fear.

“Two days after injecting graphene oxide into a specific region of the mouse’s brain, it behaved like other mice that had never experienced the smell of a cat in their home environment. In other words, graphene oxide inhibited the mouse’s anxiety-related behaviour,” Ballerini explains. She says that two days is roughly the time for memories to form and be consolidated in the mouse’s brain, which corresponds to the time for the symptoms of anxiety to subside.

“Graphene oxide interacts with the part of the brain responsible for the formation of fear-related memories, which cause anxiety. It doesn’t work like a drug, by inhibiting the function of the receptors – instead, it temporarily halts the entire mechanism long enough to disrupt the brain’s fear-related pathology, without damaging them,” continues Ballerini.

Graphene oxide interrupts anxiety-related neuron signals without affecting the neurons, or the surrounding cells. In simple terms, it only ‘turns down’ the communications between specific neurons. In a disease where these communications are over-expressed, like PTSD and anxiety, targeting the synapses with graphene oxide is enough to halt the development of this pathological behaviour. This is a type of precision medicine.

Graphene oxide is naturally eliminated after a few days, as the surrounding tissue digests the material. Ballerini says that, after two days, they did not observe any inflammation, and no traces of graphene oxide remained at all. Next, Ballerini and colleagues will seek to combine the synapse-targeting behaviour of graphene oxide with its ability to attach to carrier molecules for drug delivery.

Serge Picaud, Deputy Leader of the Graphene Flagship’s Biomedical Technologies Work Package, comments: “This work provides another great demonstration of the therapeutic potential of graphene, used either alone or included in a medical device.”

Andrea C. Ferrari, Science and Technology Officer of the Graphene Flagship and Chair of its Management Panel, adds: “The healthcare, environmental and biological applications of graphene and related materials have been investigated by the Graphene Flagship since its inception. This work opens up a new avenue of research and showcases a path for a very important therapeutic use of graphene oxide – one of the most common forms of functionalised graphene.”

References

“Biagioni, Audrey Franceschi, et al. “Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats.” Biomaterials 271 (2021): 120749.