Repetitive vibrissae-elicited forelimb placing before and immediately after unilateral 6-hydroxydopamine improves outcome in a model of Parkinson's disease
Repetitive vibrissae-elicited forelimb placing before and immediately after unilateral 6-hydroxydopamine improves outcome in a model of Parkinson's disease
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DOI：
10.1016/j.bbr.2007.01.028
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发表时间：
2007-05-16
影响因子：
2.7
通讯作者：
Roberts, David C. S.
中科院分区：
文献类型：
--
作者：
Anstrom, Kristin K.;Schallert, Timothy;Roberts, David C. S.
在帕金森病（PD）的啮齿动物模型中，在退化的早期阶段或之前立即引入的运动或复杂的生活环境可以对功能和/或神经化学结果产生有益的影响。本研究的目的是确定暴露于重复触须引起的前肢放置（一种多巴胺依赖性感觉运动）是否改善单侧输注6-OHDA的大鼠的功能结局。在将单侧6-OHDA输注到内侧前脑束中之前，将雄性Sprague-Dawley大鼠随机分成暴露于五种放置方案之一的组：（1）6-OHDA前连续两天（PRE），（2）PRE+6-OHDA后第1天，（3）PRE +6-OHDA后第1、2、3天，（4）手柄，和（5）假输注+手柄。一个会议包括180个总试验（90左前肢和90右前肢试验），包括60个连续试验，其中触须刺激诱发同侧前肢运动和30个连续试验，其中同侧前肢被限制，使触须诱发对侧前肢运动（跨中线放置）。所有组均在输注后第7天和第14天暴露于前肢放置阶段。在所有日期评估触须刺激引起6-OHDA受累前肢的同侧反应的能力。在损伤后第15天处死动物，并对黑质酪氨酸羟化酶免疫反应性（TH-ir）进行定量。与手柄组相比，重复前肢放置对所有组的行为表现都有显著影响，但只有PRE+ 123组与SHAM对照组没有显著差异。与HANDLE组相比，仅PRE+ 123组显示出TH-ir的显著保留。这些数据表明，广泛重复暴露于感觉运动任务可能会提供治疗效果的PD动物模型。(c)2007 Elsevier B. V.保留所有权利。
In rodent models of Parkinson's disease (PD), exercise or complex living environments introduced immediately before or during early stages of degeneration can provide beneficial effects on functional and/or neurochemical outcome. The goal of this study was to determine whether or not exposure to repetitive vibrissae-elicited forelimb placing, a dopamine-dependent sensorimotor movement, improves functional outcome in rats infused unilaterally with 6-OHDA. Prior to unilateral 6-OHDA infusions into the medial forebrain bundle, male Sprague-Dawley rats were randomly divided into groups exposed to one of five placing schedules: (1) two consecutive days pre-6-OHDA (PRE), (2) PRE+ day 1 post-6-OHDA, (3) PRE + days 1, 2, 3 post-6-OHDA, (4) HANDLE, and (5) Sham infusion + handle. A session consisted of 180 total trials (90 left forelimb and 90 right forelimb trials) including 60 consecutive trials where vibrissae stimulation evoked ipsilateral forelimb movement and 30 consecutive trials where the ipsilateral forelimb was restrained so that vibrissae evoked contralateral forelimb movement (cross-midline placing). All groups were exposed to forelimb placing sessions on post-infusion days 7 and 14. The ability of vibrissae stimulation to elicit an ipsilateral response of the 6-OHDA affected forelimb was assessed on all days. Animals were sacrificed on post-lesion day 15 and substantia nigra tyrosine hydroxylase immunoreactivity (TH-ir) quantified. Repetitive forelimb placing had a significant effect on behavioral performance for all groups compared to the HANDLE group, but only the PRE+ 123 group was not significantly different from SHAM controls. Only the PRE+ 123 group showed significant sparing of TH-ir compared to the HANDLE group. These data suggest that extensive repetitive exposure to a sensorimotor task may provide therapeutic effects in an animal model of PD. (c) 2007 Elsevier B.V. All rights reserved.