Galanin mediates features of neural and behavioral stress resilience afforded by exercise.

Galanin mediates features of neural and behavioral stress resilience afforded by exercise.
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DOI:
10.1016/j.neuropharm.2014.09.029
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发表时间:
2015-02
期刊:
影响因子:
4.7
通讯作者:
Holmes PV
Holmes PV
中科院分区:
医学2区
文献类型:
--
作者:
Sciolino NR;Smith JM;Stranahan AM;Freeman KG;Edwards GL;Weinshenker D;Holmes PV

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运动促进了对压力的恢复能力,并增加了蓝斑(LC)中的甘丙氨酸,但甘丙氨酸信号的变化是否介导了运动的压力缓冲作用的问题从未得到解决。为了测试丙氨酸对应激恢复能力的贡献,雄性Sprague Dawley大鼠接受脑室内(ICV)插管给药和额皮质微透析插管,并在有或没有跑步轮的情况下饲养21d。大鼠急性注射载体或丙氨酸受体拮抗剂M40,并暴露于单次足震或无应激。其他组在应激前21天长期服用甘丙肽、甘丙肽受体拮抗剂M40或载药。在应激暴露期间进行微透析取样,并于第二天在高架加迷宫中测量焦虑相关行为。用高尔基浸染法观察内侧前额叶皮层锥体神经元的树突棘,并进行定量分析。运动增加了LC中的丙氨酸水平。在非压力条件下,运动和久坐的大鼠的焦虑相关行为和多巴胺水平相当。相比之下,暴露在压力下,久坐大鼠的张开手臂探索减少,但运动大鼠或长期服用ICV甘丙肽的大鼠则没有,表明恢复力提高。运动和慢性,ICV甘丙肽阻止增加多巴胺溢出和树突棘损失观察到在久坐的大鼠应激后。慢性而非急性注射M40阻断了运动对恢复力的促进作用。结果表明,增加的丙氨酸水平促进了行为和神经水平的弹性特征。
Exercise promotes resilience to stress and increases galanin in the locus coeruleus (LC), but the question of whether changes in galanin signaling mediate the stress-buffering effects of exercise has never been addressed. To test the contributions of galanin to stress resilience, male Sprague Dawley rats received intracerebroventricular (ICV) cannulation for drug delivery and frontocortical cannulation for microdialysis, and were housed with or without a running wheel for 21d. Rats were acutely injected with vehicle or the galanin receptor antagonist M40 and exposed to a single session of either footshock or no stress. Other groups received galanin, the galanin receptor antagonist M40, or vehicle chronically for 21d prior to the stress session. Microdialysis sampling occurred during stress exposure and anxiety-related behavior was measured on the following day in the elevated plus maze. Dendritic spines were visualized by Golgi impregnation in medial prefrontal cortex (mPFC) pyramidal neurons and quantified. Exercise increased galanin levels in the LC. Under non-stressed conditions, anxiety-related behavior and dopamine levels were comparable between exercised and sedentary rats. In contrast, exposure to stress reduced open arm exploration in sedentary rats but not in exercise rats or those treated chronically with ICV galanin, indicating improved resilience. Both exercise and chronic, ICV galanin prevented the increased dopamine overflow and loss of dendritic spines observed after stress in sedentary rats. Chronic, but not acute M40 administration blocked the resilience-promoting effects of exercise. The results indicate that increased galanin levels promote features of resilience at both behavioral and neural levels.
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