Research on the pathophysiological roles of TRP channels on the neuron-glia interactions in central nervous system disorder

神经元和胶质细胞之间的相互作用在中枢神经系统疾病的发病机制中的重要性正在被揭示和理解；然而，Trp通道在神经元-胶质细胞信号转导中的病理生理作用仍有待阐明。本研究主要研究TRPC3在星形胶质细胞中的表达，以及TRPV4和TRPM2在小胶质细胞中的表达。体外和体内实验表明：1)TRPC3抑制剂PYR3改善小鼠脑出血后的预后，减轻星形胶质细胞增生；2)TRPV4通道的开放减弱了细胞外钙的驱动力，抑制了小胶质细胞的激活；3)TRPM2可能通过巨噬细胞/小胶质细胞释放NO来介导脑缺血损伤。上述结果提示，上述Trp通道可能成为中枢神经系统疾病治疗的新靶点。

The importance of interactions between neurons and glia in the pathogenesis of CNS disorders is becoming revealed and understood; however the pathophysiological roles of TRP channels in neuron-glia signaling remain to be elucidated. This study focused on TRPC3 expressed in astrocyte and TRPV4 and TRPM2 expressed in microglia. In vitro and in vivo experiments demonstrate that 1) TRPC3 inhibitor Pyr3 improves outcomes and attenuates astrogliosis after intracerebral hemorrhage in mice, 2) the opening of TRPV4 channel attenuates the driving force for extracellular Ca2+ and suppresses microglial activation, 3) TRPM2 could mediate the cerebral ischemic injury through NO release from macrophage/microglia. These results suggest that the above-mentioned TRP channelsmay constitute a new therapeutic target for CNS disorders.