Involuntary, Forced and Voluntary Exercises Equally Attenuate Neurocognitive Deficits in Vascular Dementia by the BDNF-pCREB Mediated Pathway
Involuntary, Forced and Voluntary Exercises Equally Attenuate Neurocognitive Deficits in Vascular Dementia by the BDNF-pCREB Mediated Pathway
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DOI：
10.1007/s11064-015-1673-3
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发表时间：
2015-09-01
影响因子：
4.4
通讯作者：
Lu, Xinxin
中科院分区：
文献类型：
--
作者：
Lin, Yangyang;Lu, Xiao;Lu, Xinxin
采用血管性痴呆大鼠模型，比较功能性电刺激诱导的不自主运动、强迫运动和自主运动对认知功能恢复的影响及其机制。不自主运动组（I-EX）采用FES诱发大鼠以12 m/min的速度在梯子上进行不自主步态跑，强迫运动组（F-EX）和自主运动组（V-EX）采用跑轮运动。使用巴恩斯迷宫进行行为评估。采用免疫组织化学方法检测海马CA 1、CA 2/3和齿状回（DG）区脑源性神经营养因子（BDNF）、磷酸化细胞外信号调节激酶1和2（ERK 1/2）和cAMP反应元件结合蛋白（CREB）的表达。Western blotting检测海马和前额皮质BDNF、磷酸化蛋白激酶B（Akt）、原肌球蛋白受体激酶B（Trk B）、丝裂原活化蛋白激酶1和2（MEK 1/2）、ERK 1/2和CREB在BDNF-pCREB信号通路中的表达。无意识的，强迫的和自愿的运动都被发现可以逆转血管性痴呆的认知缺陷，效果大致相同。3个运动组海马CA 1、CA 2/3和DG区BDNF、pCREB和pERK 1/2免疫阳性细胞数均显著增加。此外，不自主运动激活BDNF和磷酸化的Akt，TrkB，MEK 1/2，ERK 1/2和CREB在海马和前额叶皮层同样自愿或强迫运动。这些结果表明，FES诱导的不自主运动可能有利于减轻脑缺血后的认知功能障碍。
A rat model of vascular dementia was used to compare the effects of involuntary exercise induced by functional electrical stimulation (FES), forced exercise and voluntary exercise on the recovery of cognitive function recovery and its underlying mechanisms. In an involuntary exercise (I-EX) group, FES was used to induce involuntary gait-like running on ladder at 12 m/min. A forced exercise group (F-EX) and a voluntary exercise group (V-EX) exercised by wheel running. The Barnes maze was used for behavioral assessment. Brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element binding protein (CREB) positive cells in hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were evaluated using immunohistochemical methods. Western blotting was used to assess the levels of BDNF, phosphorylated protein kinase B (Akt), tropomyosin receptor kinase B (TrkB), mitogen-activated protein kinase 1 and 2 (MEK1/2), ERK1/2 and CREB in BDNF-pCREB signaling in the hippocampus and prefrontal cortex. Involuntary, forced and voluntary exercises were all found to reverse the cognitive deficits of vascular dementia with about equal effectiveness. The number of BDNF, pCREB and pERK1/2 immunopositive cells was significantly increased in the hippocampal CA1, CA2/3 and DG regions in all three exercise groups. In addition, involuntary exercise activated BDNF and the phosphorylation of Akt, TrkB, MEK1/2, ERK1/2 and CREB in the hippocampus and prefrontal cortex equally as well as voluntary or forced exercise. These results suggest that involuntary exercise induced by FES may be as beneficial for alleviating cognitive deficits after cerebral ischemia.