Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
Genes Brain Behav. 2012 Jul;11(5):529-38. doi: 10.1111/j.1601-183X.2012.00788.x. Epub 2012 May 3.
Exercise, specifically voluntary wheel running, is a potent stimulator of hippocampal neurogenesis in adult mice. In addition, exercise induces behavioral changes in numerous measures of anxiety in rodents. However, the physiological underpinnings of these changes are poorly understood. To investigate the role of neurogenesis in exercise-mediated anxiety, we examined the cellular and behavioral effects of voluntary wheel running in mice with a reduction in hippocampal neurogenesis, achieved through conditional deletion of ataxia telangiectasia-mutated and rad-3-related protein (ATR), a cell cycle checkpoint kinase necessary for normal levels of neurogenesis. Following hippocampal microinjection of an adeno-associated virus expressing Cre recombinase to delete ATR, mice were exposed to 4 weeks of voluntary wheel running and subsequently evaluated for anxiety-like behavior. Wheel running resulted in increased cell proliferation and neurogenesis, as measured by bromodeoxyuridine and doublecortin, respectively. Wheel running also resulted in heightened anxiety in the novelty-induced hypophagia, open field and light-dark box tests. However, both the neurogenic and anxiogenic effects of wheel running were attenuated following hippocampal ATR deletion, suggesting that increased neurogenesis is an important mediator of exercise-induced anxiety.
锻炼，特别是自愿轮式跑步，是成年老鼠海马神经发生的有力刺激物。此外，锻炼会引起啮齿动物在许多焦虑措施中的行为变化。然而，这些变化的生理基础还知之甚少。为了研究神经发生在锻炼介导的焦虑中的作用，我们研究了通过条件性敲除共济失调毛细血管扩张突变和 rad-3 相关蛋白 (ATR) 来减少海马神经发生的情况下，自愿轮式跑步对小鼠的细胞和行为影响，ATR 是一种细胞周期检查点激酶，对于正常水平的神经发生是必需的。在海马内注射表达 Cre 重组酶的腺相关病毒以敲除 ATR 后，将小鼠暴露于 4 周的自愿轮式跑步中，然后评估其焦虑样行为。轮式跑步导致细胞增殖和神经发生增加，分别通过溴脱氧尿苷和双皮质蛋白测量。轮式跑步还导致新奇诱导的摄食量减少、旷场和明暗箱测试中的焦虑增加。然而，在海马 ATR 敲除后，轮式跑步的神经发生和焦虑作用都减弱了，这表明增加的神经发生是锻炼引起焦虑的一个重要介导物。
