Exercise-Induced Cognitive Improvement Is Associated with Sodium Channel-Mediated Excitability in APP/PS1 Mice
Autor: | Shan Li, Xu-Yang Wang, Zhang Li, Min-Nan Lu, Guang-Cai Liu, Rong Mei, Rui Mao, Tan Yaxin, Bo Chen, Tao Hu, Hong-Lan Chen, Xi-Yang Yanbin |
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Rok vydání: | 2020 |
Předmět: |
Genetically modified mouse
Article Subject Morris water navigation task Neurosciences. Biological psychiatry. Neuropsychiatry Mice Transgenic Physical exercise Motor Activity Hippocampal formation Electroencephalography Sodium Channels Mice 03 medical and health sciences Cognition 0302 clinical medicine Alzheimer Disease Memory Physical Conditioning Animal Amyloid precursor protein Animals Medicine 030304 developmental biology 0303 health sciences biology medicine.diagnostic_test business.industry Sodium channel Brain Mice Inbred C57BL Disease Models Animal Neurology biology.protein Female Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery RC321-571 Research Article |
Zdroj: | Neural Plasticity Neural Plasticity, Vol 2020 (2020) |
ISSN: | 1687-5443 2090-5904 |
Popis: | 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. |
Databáze: | OpenAIRE |
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