Exercise-Induced Cognitive Improvement Is Associated with Sodium Channel-Mediated Excitability in APP/PS1 Mice
Exercise-Induced Cognitive Improvement Is Associated with Sodium Channel-Mediated Excitability in APP/PS1 Mice
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APP/PS1 小鼠运动引起的认知改善与钠通道介导的兴奋性相关
DOI：
10.1155/2020/9132720
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发表时间：
2020-03
影响因子：
3.1
通讯作者：
Xiyang Yan-Bin
中科院分区：
文献类型：
--
作者：
Tan Ya-Xin;Liu Guang-Cai;Chen Hong-Lan;Lu Min-Nan;Chen Bo;Hu Tao;Zhang Li;Mao Rui;Li Shan;Mei Rong;Wang Xu-Yang;Xiyang Yan-Bin
大脑活动升高或过度兴奋会导致认知障碍，并增加患阿尔茨海默病 (AD) 的风险。阻止神经网络的过度激励可能是预防、阻止甚至逆转这种情况的一种有前途的新策略。体育锻炼已被证明是一种有效的认知增强剂，可以降低老年人患 AD 的风险，但其潜在机制还远未完全了解。我们探讨了长期跑步机运动是否会减弱淀粉样前体蛋白（APP）/早老素-1（PS1）突变诱导的异常网络活动，从而通过改变转基因小鼠中电压门控钠通道（Nav）的数量和/或分布来改善认知。对2、3.5、5、6.5、8和9个月龄的APP/PS1小鼠进行不同持续时间或AD不同阶段的跑步机运动。评估了记忆、脑电图 (EEG) 记录以及 Nav 功能成员（Nav1.1α、Nav1.2、Nav1.6 和 Navβ2）的表达水平和分布的变化。结果显示，持续 12 周和 24 周的跑步机锻炼 1) 可显着改善新物体识别 (NOR) 记忆和莫里斯水迷宫 (MWM) 空间记忆； 2) 部分减少异常尖峰活性； 3) 纠正 Nav1.1α 的细胞分布紊乱、异常的 Navβ2 裂解增强和 Nav1.6 上调。此外，24周运动组的APP/PS1小鼠在NOR任务中表现出更好的表现，并且Nav1.6表达大幅下降，接近野生型水平。这项研究表明，运动通过改变 APP/PS1 小鼠海马 Nav 的数量和分布来改善认知和神经活动。从临床前阶段开始进行约 24 周的长期跑步机锻炼是预防 AD 并阻止其进展的一种有前途的治疗策略。
Elevated brain activation, or hyperexcitability, induces cognitive impairment and confers an increased risk of Alzheimer's disease (AD). Blocking the overexcitation of the neural network may be a promising new strategy to prevent, halt, and even reverse this condition. Physical exercise has been shown to be an effective cognitive enhancer that reduces the risk of AD in elderly individuals, but the underlying mechanisms are far from being fully understood. We explored whether long-term treadmill exercise attenuates amyloid precursor protein (APP)/presenilin-1 (PS1) mutation-induced aberrant network activity and thus improves cognition by altering the numbers and/or distribution of voltage-gated sodium channels (Nav) in transgenic mice. APP/PS1 mice aged 2, 3.5, 5, 6.5, 8, and 9 months underwent treadmill exercise with different durations or at different stages of AD. The alterations in memory, electroencephalogram (EEG) recordings, and expression levels and distributions of Nav functional members (Nav1.1α, Nav1.2, Nav1.6, and Navβ2) were evaluated. The results revealed that treadmill exercise with 12- and 24-week durations 1) induced significant improvement in novel object recognition (NOR) memory and Morris water maze (MWM) spatial memory; 2) partially reduced abnormal spike activity; and 3) redressed the disturbed cellular distribution of Nav1.1α, aberrant Navβ2 cleavage augmentation, and Nav1.6 upregulation. Additionally, APP/PS1 mice in the 24-week exercise group showed better performance in the NOR task and a large decrease in Nav1.6 expression, which was close to the wild-type level. This study suggests that exercise improves cognition and neural activity by altering the numbers and distribution of hippocampal Nav in APP/PS1 mice. Long-term treadmill exercise, for about 24 weeks, starting in the preclinical stage, is a promising therapeutic strategy for preventing AD and halting its progress.
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DOI：
10.1016/s0006-291x(04)00995-7
发表时间：
2004-06
影响因子：
3.1
作者：
Kausalia Vijayaragavan
通讯作者：
Kausalia Vijayaragavan
影响因子：
9.3
作者：
Littlefield AM;Setti SE;Priester C;Kohman RA
通讯作者：
Kohman RA
影响因子：
48
作者：
Kalaria, Raj N.;Maestre, Gladys E.;Arizaga, Raul;Friedland, Robert P.;Galasko, Doug;Hall, Kathleen;Luchsinger, Jose A.;Ogunniyi, Adesola;Perry, Elaine K.;Potocnik, Felix;Prince, Martin;Stewart, Robert;Wimo, Anders;Zhang, Zhen-Xin;Antuono, Piero
通讯作者：
Antuono, Piero
影响因子：
--
作者：
D. Ragsdale
通讯作者：
D. Ragsdale
影响因子：
37.8
作者：
J. Malhotra;Chunling Chen;I. Rivolta;Hugues Abriel;R. Malhotra;L. N. Mattei;F. Brosius;R. Kass;L. Isom
通讯作者：
J. Malhotra;Chunling Chen;I. Rivolta;Hugues Abriel;R. Malhotra;L. N. Mattei;F. Brosius;R. Kass;L. Isom