Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- lesioned mouse basal ganglia
Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- lesioned mouse basal ganglia
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DOI：
10.1002/jnr.20162
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发表时间：
2004-08-01
影响因子：
4.2
通讯作者：
Jakowec, MW
中科院分区：
文献类型：
--
作者：
Fisher, BE;Petzinger, GM;Jakowec, MW
体力活动已被证明是影响基底神经节病变的神经保护。采用踏车运动模式，我们研究了运动对神经恢复的影响。1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）损伤的小鼠模型提供了一种研究运动对神经恢复的影响的方法，因为30-40%的黑质纹状体多巴胺能神经元在MPTP损伤后存活，并且可以为神经恢复的发生提供模板。给MPTP损伤的C57 BL/6 J小鼠施用MPTP（四次注射20 mg/kg游离碱，间隔2小时）或盐水，并分成以下组：（1）盐水;（2）盐水+运动;（3）MPTP;和（4）MPTP +运动。运动组小鼠在MPTP损伤后4天开始在电动跑步机上跑步30天（MPTP诱导的细胞死亡完成后的一段时间）。最初，MPTP损伤+运动小鼠与盐水+运动小鼠相比以较慢的速度跑较短的时间。MPTP +运动组的速度和耐力在30天的运动期内都提高到接近正常水平。参与基底神经节功能的蛋白质和基因的表达，包括多巴胺转运蛋白（DAT），酪氨酸羟化酶（TH），多巴胺D1和D2受体，以及谷氨酸免疫标记的改变进行了测定。运动导致纹状体DAT的显着下调MPTP +运动相比MPTP nonexercised小鼠和在较小程度上在盐水+运动小鼠相比，他们没有运动的同行。研究结束时，MPTP和MPTP +运动组之间的TH蛋白水平无显著差异。生理盐水+运动组纹状体多巴胺D1和D2受体mRNA转录本的表达受到抑制;而MPTP +运动组小鼠纹状体多巴胺D2转录本的表达增加。免疫电子显微镜检查表明，跑步机运动逆转了MPTP给药后神经末梢谷氨酸免疫标记的损伤诱导增加。我们的数据表明，运动通过调节对基底神经节功能重要的基因和蛋白质来促进受损大脑的行为恢复。(C)2004 Wiley-Liss，Inc.
Physical activity has been shown to be neuroprotective in lesions affecting the basal ganglia. Using a treadmill exercise paradigm, we investigated the effect of exercise on neuro restoration. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model provides a means to investigate the effect of exercise on neurorestoration because 30-40% of nigrostriatal dopaminergic neurons survive MPTP lesioning and may provide a template for neurorestoration to occur. MPTP-lesioned C57 BL/6J mice were administered MPTP (four injections of 20 mg/kg free-base, 2 hr apart) or saline and divided into the following groups: (1) saline; (2) saline + exercise; (3) MPTP; and (4) MPTP + exercise. Mice in exercise groups were run on a motorized treadmill for 30 days starting 4 days after MPTP lesioning (a period after which MPTP-induced cell death is complete). Initially, MPTP-lesioned + exercise mice ran at slower speeds for a shorter amount of time compared to saline + exercise mice. Both velocity and endurance improved in the MPTP + exercise group to near normal levels over the 30-day exercise period. The expression of proteins and genes involved in basal ganglia function including the dopamine transporter (DAT), tyrosine hydroxylase (TH), and the dopamine D1 and D2 receptors, as well as alterations on glutamate immunolabeling were determined. Exercise resulted in a significant downregulation of striatal DAT in the MPTP + exercise compared to MPTP nonexercised mice and to a lesser extent in the saline + exercised mice compared to their no-exercise counterparts. There was no significant difference in TH protein levels between MPTP and MPTP + exercise groups at the end of the study. The expression of striatal dopamine D1 and D2 receptor mRNA transcript was suppressed in the saline + exercise group; however, dopamine D2 transcript expression was increased in the MPTP + exercise mice. Immunoelectron microscopy indicated that treadmill exercise reversed the lesioned-induced increase in nerve terminal glutamate immunolabeling seen after MPTP administration. Our data demonstrates that exercise promotes behavioral recovery in the injured brain by modulating genes and proteins important to basal ganglia function. (C) 2004 Wiley-Liss, Inc.