Glucocorticoid signaling and exercise-induced downregulation of the mineralocorticoid receptor in the induction of adult mouse dentate neurogenesis by treadmill running
Glucocorticoid signaling and exercise-induced downregulation of the mineralocorticoid receptor in the induction of adult mouse dentate neurogenesis by treadmill running
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DOI：
10.1016/j.psyneuen.2008.05.014
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发表时间：
2008-10-01
影响因子：
3.7
通讯作者：
Kuo, Yu-Min
中科院分区：
文献类型：
--
作者：
Chang, Ya-Ting;Chen, Yi-Chieh;Kuo, Yu-Min
体育锻炼可以促进成人神经发生，但其潜在机制尚不清楚。糖皮质激素（啮齿类动物的皮质酮）是一种已知影响神经发生的因子。由于体育锻炼调节皮质酮分泌，我们假设皮质酮信号参与运动诱导的成人神经发生。我们选择跑步机跑步（TR）来准确定义运动的强度和持续时间。结果表明，5周的TR增加了成年海马中双皮质素（DCX）阳性神经元祖细胞（NPC），并在TR方案结束时短暂增加了血清皮质酮水平。该方案降低了海马盐皮质激素受体（MR）的水平;然而，糖皮质激素受体水平没有改变。然后，我们研究是否减少皮质酮水平双侧肾上腺切除术（ADX）衰减TR增强成人神经发生。我们的结果表明，ADX不仅阻断TR诱导的MR下调，而且减少TR增强的NPC的数量。为了研究MR下调在TR诱导的成年神经发生中的作用，用选择性MR拮抗剂螺内酯重复治疗动物3周。结果表明，螺内酯可增加齿状区自发发生和TR诱导的NPC数量。进一步的分析表明，螺内酯治疗没有改变前体细胞增殖，但增加了DCX阳性NPC的数量，这表明MR信号传导的阻断促进祖细胞向神经元的分化和/或增强NPC的存活。综上所述，数据表明TR诱导成年海马齿状区的NPC部分是由于糖皮质激素/MR信号转导的下调，其随后增强了沿着神经元谱系的分化和/或NPC存活。(C)2008爱思唯尔有限公司保留所有权利。
Physical exercise is known to promote adult neurogenesis, although the underlying mechanisms remain unclear. Glucocorticoid (corticosterone in rodents) is a factor that is known to affect neurogenesis. As physical exercise modulates corticosterone secretion, we hypothesized that corticosterone signaling is involved in exercise-induced adult neurogenesis. We chose treadmill running (TR) to accurately define the intensity and duration of exercise. Our results showed that 5 weeks of TR increased the doublecortin (DCX)-positive neuronal progenitor cells (NPCs) in adult hippocampus and transiently increased the serum corticosterone Level at the end of the TR protocol. This protocol reduced the Levels of hippocampal mineralocorticoid receptor (MR); however, glucocorticoid receptor Levels were unaltered. We then investigated whether reducing corticosterone levels by bilateral adrenalectomy (ADX) attenuated the TR-enhanced adult neurogenesis. Our results showed that ADX not only blocked the TR-induced downregulation of MR, but also reduced the number of TR-enhanced NPCs. In order to examine the role of MR downregulation in TR-induced adult neurogenesis, animals were treated repeatedly with a selective MR antagonist, spironolactone, for 3 weeks. The results revealed that spironolactone increased the number of spontaneously occurring and TR-induced NPC in the dentate area. Further analysis revealed that spironolactone treatment did not alter precursor cell proliferation, but increased the number of DCX-positive NPCs, suggesting that blockage of MR signaling either facilitates the differentiation of progenitor cells towards neurons and/or enhances the survival of NPCs. Taken together, the data indicated that induction of NPCs in the dentate area of adult hippocampus by TR is partly due to the downregutation of glucocorticoid/MR signaling, which subsequently enhances differentiation along a neuronal Lineage and/or NPC survival. (C) 2008 Elsevier Ltd. All rights reserved.