Increase in membrane surface expression and phosphorylation of TRPC3 related to olfactory dysfunction in α-synuclein transgenic mice.

Olfactory impairment is an initial non-motor symptom of Parkinson's disease that causes the deposition of aggregated α-synuclein (α-syn) in olfactory neurons. Transient receptor potential canonical (TRPC) channels are a diverse group of non-selective Ca entry channels involved in the progression or pathogenesis of PD via Ca homeostatic regulation. However, the relationship between TRPC and α-syn pathology in an olfactory system remains unclear. To address this issue, we assessed the olfactory function in α-syn transgenic mice. In contrast with control mice, the transgenic mice exhibited impaired olfaction, TRPC3 activation and apoptotic neuronal cell death in the olfactory system. Similar results were observed in primary cultures of olfactory neurons, that is TRPC3 activation, increasing intracellular Ca concentration and apoptotic cell death in the α-syn-overexpressed neurons. These changes were significantly attenuated by TRPC3 knockdown. Therefore, our findings suggest that TRPC3 activation and calcium dyshomeostasis play a key role in α-syn-induced olfactory dysfunction in mice.