Department of Anatomy and Neuroscience, University College Cork, Ireland.
APC Microbiome Institute, University College Cork, Ireland.
Hippocampus. 2018 Jan;28(1):3-11. doi: 10.1002/hipo.22805. Epub 2017 Oct 13.
Adolescence is a sensitive period of neurodevelopment during which life experiences can have profound effects on the brain. Hippocampal neurogenesis, the neurodevelopmental process of generating functional new neurons from neural stem cells, occurs throughout the lifespan and has been shown to play a role in learning, memory and in mood regulation. In adulthood it is influenced by extrinsic environmental factors such as exercise and stress. Intrinsic factors that regulate hippocampal neurogenesis include the orphan nuclear receptor TLX (Nr2e1) which is primarily expressed in the neurogenic niches of the brain. While mechanisms regulating adult hippocampal neurogenesis have been widely studied, less is known on how hippocampal neurogenesis is affected during adolescence. The aim of this study was to investigate the influence of both TLX and isolation stress on exercise-induced increases in neurogenesis in running and sedentary conditions during adolescence. Single- (isolation stress) wild type and Nr2e1 mice or pair-housed wild type mice were housed in sedentary conditions or allowed free access to running wheels for 3 weeks during adolescence. A reduction of neuronal survival was evident in mice lacking TLX, and exercise did not increase hippocampal neurogenesis in these Nr2e1 mice. This suggests that TLX is necessary for the pro-neurogenic effects of exercise during adolescence. Interestingly, although social isolation during adolescence did not affect hippocampal neurogenesis, it prevented an exercise-induced increase in neurogenesis in the ventral hippocampus. Together these data demonstrate the importance of intrinsic and extrinsic factors in promoting an exercise-induced increase in neurogenesis at this key point in life.
青春期是大脑神经发育的敏感时期，生活经历在此期间可能对大脑产生深远的影响。海马神经发生是指从神经干细胞产生功能性新神经元的神经发育过程，它贯穿于整个生命过程，并被证明在学习、记忆和情绪调节中发挥作用。在成年期，它受到外在环境因素（如运动和压力）的影响。调节海马神经发生的内在因素包括孤儿核受体 TLX（Nr2e1），它主要在大脑的神经发生龛中表达。虽然调节成年海马神经发生的机制已被广泛研究，但对于青春期海马神经发生如何受到影响知之甚少。本研究旨在探讨 TLX 和隔离应激对青春期在跑步和久坐两种状态下，运动诱导的神经发生的影响。单（隔离应激）野生型和 Nr2e1 小鼠或同笼饲养的野生型小鼠在青春期时分别处于久坐状态或可自由使用跑步轮 3 周。Nr2e1 小鼠中神经元存活减少，运动也没有增加海马神经发生，这表明 TLX 是运动对青春期神经发生的促神经发生作用所必需的。有趣的是，尽管青春期的社会隔离并不影响海马神经发生，但它阻止了运动在腹侧海马区诱导的神经发生增加。这些数据共同表明内在和外在因素在促进生命关键时期的运动诱导神经发生中具有重要作用。
