PRNP and mood disorder: PrPc may play a role in the pathophysiology of mood disorders through its significant role in long-term depression (LTD), a critical cellular mechanism responsible for synaptic plasticity and neuroprotection against excitotoxicity in the cerebellum [91,92] Transgenic mice with knock-out of PrPc gene (Ngsk Prnp−/−) presented impaired LTD in excitatory synaptic transmission at connections between parallel fibers and Purkinje cells.