Graphene oxide nanoflakes enable targeting dysfunctional synaptic plasticity in the amygdala

In the last decade, graphene-based nanomaterials (GBNs) have been proposed as innovative therapeutic tools in the field of precision medicine for neuroscience applications (Kostarelos K. et al., 2017; Bramini M. et al., 2018; Cellot G. et al., 2022). In detail, graphene oxide (GO) nanoflakes with small lateral dimension (s-GO) were found to target specifically and transiently glutamatergic synapses of the hippocampus in vivo, by reducing the release of neurotransmitter from the presynaptic terminal (Rauti et al., 2019). Recently, it has been suggested that this precise targeting of excitatory synapses could be applied to rescue the aberrant glutamatergic transmission characterizing several brain diseases, from dementia to anxiety disorders. Among these, posttraumatic stress disorder (PTSD) is related to a hyper-function of the lateral amygdala (LA), a nucleus involved in the storage of aversive memory induced by stressful events, resulting in longterm potentiation (LTP) of glutamatergic synapses (Parsons M.P. et al., 2014). In this framework, in my thesis I have addressed the following issues: (i) To investigate if s-GO could be used to hamper the aberrantly increased glutamatergic transmission observed in pathological conditions, such as in the PTSD; (ii) to identify the subcellular target of s-GO in order to dissect the mechanism of interaction between the nanomaterial and potentiated synapses; (iii) to explore the potential of s-GO as nanocarrier in drug delivery systems, by using neuropeptide Y (NPY) as carried biologically active molecule.