Transient Receptor Potential Vanilloid 6 Modulates Aberrant Axonal Sprouting in a Mouse Model of Pilocarpine-Induced Epilepsy

Abstract

Transient receptor potential vanilloid 6 (TRPV6) is a highly selective calcium-ion channel that belongs to the TRPV family. TRPV6 is widely distributed in the brain, but its role in neurological diseases such as epilepsy remains unknown. Here, we report for the first time that TRPV6 expression is upregulated in the hippocampus of a pilocarpine-induced status epilepticus model, mainly in the suprapyramidal bundle of the mossy fiber (MF) projection of the hippocampal CA3 regions. We found that TRPV6 overexpression via viral vector transduction attenuated abnormal MF sprouting (MFS), whereas TRPV6 knockdown aggravated the development of MFS and the incidence of recurrent seizures during epileptogenic progression. In the in vitro experiments, our results showed that modulation of TRPV6 expression resulted in a change in axonal formation in cultured hippocampal neurons. In addition, we found that TRPV6 was implicated in the regulation of Akt-glycogen synthase kinase-3-β activity, which is closely related to the cellular mechanism of axonal outgrowth. Therefore, these findings suggest that TRPV6 may regulate the formation of aberrant synaptic circuits during epileptogenesis.