GDAP2 Overexpression Affects the Development of Neurons and Dysregulates Neuronal Excitatory Synaptic Transmission

GDAP2 is a gene highly expressed in the human brain and encodes ganglioside-induced differentiation-associated protein 2 (GDAP2). At present, little is known about the function of GDAP2. In recent years, it has been reported that mutations in the GDAP2 gene may be involved in hereditary cerebellar ataxia. In this study, we first conducted a preliminary study on the effect of GDAP2 overexpression on cultured primary hippocampal neurons in vitro. By analysing neuronal morphology, it was found that the complexity of neurons and the number of dendritic spines increased when GDAP2 was upregulated. The electrophysiological recordings showed that GDAP2 overexpression significantly increased the frequency of mEPSCs, suggesting that GDAP2 overexpression dysregulates excitatory synaptic transmission in cultured primary hippocampal neurons in vitro. On the other hand, behavioural and field-potential recordings of epileptic mouse models showed that GDAP2 overexpression was associated with increased seizure frequency. In summary, this preliminary study suggested that GDAP2 overexpression may have a certain pathogenic effect, providing a new perspective for the study of gene-related diseases such as epilepsy.