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

神经元和神经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的重要性正在被揭示和理解，但TRP通道在神经元-神经胶质细胞信号传导中的病理生理作用仍有待阐明。本研究主要关注星形胶质细胞中表达的TRPC 3和小胶质细胞中表达的TRPV 4和TRPM 2。体内外实验结果表明：1）TRPC 3抑制剂Pyr 3可改善小鼠脑出血后的预后并抑制星形胶质细胞增生; 2）TRPV 4通道开放可减弱细胞外Ca 2+驱动力并抑制小胶质细胞活化; 3）TRPM 2可通过巨噬细胞/小胶质细胞释放NO介导脑缺血损伤。这些结果提示上述TRP通道可能成为治疗中枢神经系统疾病的新靶点。

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.