Abstract：
Exercise can promote adult neurogenesis and improve symptoms associated with schizophrenia and other mental disorders via parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus ErbB4 is the receptor of neurotrophic factor neuregulin 1, expressed mostly in PV-positive interneurons. Whether ErbB4 in PV-positive neurons mediates the beneficial effect of exercise and adult neurogenesis on mental disorder needs to be further investigation. Here, we first conducted a four-week study on the effects of AG1478, an ErbB4 inhibitor, on memory and neurogenesis. AG1478 significantly impaired the performance in several memory tasks, including the T-maze, Morris water maze, and contextual fear conditioning, downregulated the expression of total ErbB4 (T-ErbB4) and the ratio of phosphate-ErbB4 (p-ErbB4) to T-ErbB4, and associated with neurogenesis impairment. Interestingly, AG1478 also appeared to decrease intracellular calcium levels in PV neurons, which could be reversed by exercise. These results suggest exercise may regulate adult neurogenesis and PV neuron activity through ErbB4 signaling. Overall, these findings provide further evidence of the importance of exercise for neurogenesis and suggest that targeting ErbB4 may be a promising strategy for improving memory and other cognitive functions in individuals with mental disorders.
摘要：
运动可以通过齿状回中的小白蛋白（PV）阳性GABA能中间神经元促进成人神经发生并改善与精神分裂症和其他精神障碍相关的症状ErbB4是神经营养因子神经调节素1的受体，主要在PV阳性中间神经元中表达。PV阳性神经元中的ErbB4是否介导运动和成人神经发生对精神障碍的有益作用需要进一步研究。这里,我们首先对ErbB4抑制剂AG1478的作用进行了为期四周的研究，关于记忆和神经发生。AG1478在几个内存任务中显著削弱了性能，包括T迷宫,莫里斯水迷宫，和上下文恐惧条件，下调总ErbB4（T-ErbB4）的表达和磷酸盐ErbB4（p-ErbB4）与T-ErbB4的比例，并与神经发生障碍有关。有趣的是,AG1478也似乎降低PV神经元的细胞内钙水平，这可以通过锻炼来逆转。这些结果表明运动可能通过ErbB4信号调节成人神经发生和PV神经元活性。总的来说,这些发现为运动对神经发生的重要性提供了进一步的证据,并提示靶向ErbB4可能是改善精神障碍患者记忆和其他认知功能的有前景的策略.
