Treadmill exercise improves behavioral outcomes and spatial learning memory through up-regulation of reelin signaling pathway in autistic rats.
Treadmill exercise improves behavioral outcomes and spatial learning memory through up-regulation of reelin signaling pathway in autistic rats.
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DOI：
10.12965/jer.130003
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发表时间：
2013-04
影响因子：
1.9
通讯作者：
Baek SS
中科院分区：
文献类型：
--
作者：
Seo TB;Cho HS;Shin MS;Kim CJ;Ji ES;Baek SS
自闭症是一种复杂的神经发育障碍，具有社会互动和沟通障碍，以及重复性行为障碍。Reelin是一种细胞外糖蛋白，对神经元迁移和大脑发育至关重要。运动对各种脑损伤的神经保护作用已被充分证明，然而，运动对自闭症的影响与reelin表达的关系尚不清楚。在本研究中，我们研究了跑步机运动对自闭症大鼠功能恢复的影响以及对reelin及其下游分子磷脂酰肌醇-3激酶（PI3K）、磷酸化Akt （p-Akt）、磷酸化细胞外信号调节蛋白激酶1和2 （p-ERK1/2）表达的影响。在大鼠出生后第14天皮下注射400 mg/kg丙戊酸，建立自闭症样动物模型。从出生后第28天开始，每天1次，每周5次，连续4周在跑步机上跑步30分钟。为了研究自闭症样行为与记忆缺陷的关系，采用开放视野、社会互动和径向八臂迷宫等方法。进行免疫组织化学和免疫印迹检测。在本研究结果中，跑步机运动减轻了自闭症大鼠空间学习记忆的攻击倾向，提高了空间学习记忆的正确决策。跑步机运动增加自闭症大鼠海马神经发生和reelin及其下游分子PI3K、p-Akt和p-ERK1/2的表达。本研究表明，跑步机运动可通过激活旋回信号通路改善自闭症大鼠的攻击行为和空间学习记忆。
Autism is a complex neurodevelopmental disability with impairments of social interaction and communication, and repetitive behavior. Reelin is an extracellular glycoprotein that is essential for neuronal migration and brain development. Neuroprotective effects of exercise on various brain insults are well documented, however, the effects of exercise on autism in relation with reelin expression are not clarified. In the present study, we investigated the effects of treadmill exercise on the functional recovery and on the expressions of reelin and its downstream molecules, phosphatidylinositol-3-kinase (PI3K), phosphorylated Akt (p-Akt), phosphorylated extracellular signal-regulated protein kinase 1 and 2 (p-ERK1/2), using autistic rats. For the induction of autism-like animal model, 400 mg/kg valproic acid was subcutaneously injected into the rats on the postnatal day 14. The rat in the treadmill exercise groups were forced to run on a treadmill for 30 min once a day, five times a week for 4 weeks, starting postnatal day 28. To investigate autism-like behaviors and memory deficit, open field, social interaction, and radial 8-arm maze were performed. Immunohistochemistry and western blotting were conducted. In the present results, treadmill exercise alleviated aggressive tendency and improved correct decision in the spatial learning memory in the autistic rats. Treadmill exercise increased neurogenesis and the expressions of reelin and its down-stream molecules, PI3K, p-Akt, and p-ERK1/2, in the hippocampus of the autistic rats. The present study showed that treadmill exercise ameliorated aggressive behavior and improved spatial learning memory through activation of reeling signaling pathway in the valproic acid-induced autistic rats.