title: High-intensity treadmill running impairs cognitive behavior and hippocampal synaptic plasticity of rats via activation of inflammatory response.
abstract: Although appropriate exercise is beneficial for enhancing brain functions, high-intensity exercise (HIE)-induced cognitive dysfunction is causing more and more concerns nowadays. In the present study, we observed the effects of high-intensity treadmill running on the spatial learning of the adult Sprague Dawley male rats in Y-maze (n = 16 per group), and investigated its possible electrophysiological and molecular mechanisms by examining in vivo hippocampal long-term potentiation (LTP), central inflammatory responses, and JNK/p38/ERK signal pathway. The Y-maze active avoidance test showed that high-intensity treadmill running impaired spatial learning ability of rats, with increased error times and prolonged training time in recognizing safety condition. Associated with the cognitive dysfunction, the induction and maintenance of hippocampal LTP were also impaired by the HIE. Furthermore, accompanied by elevated levels of inflammatory factors IL-1β, TNF-α, and iNOS, overactivation of microglia and astrocytes was also found in the CA1 region of hippocampus in the excessive exercise group, indicating an inflammatory response induced by HIE. In addition, Western blot assay showed that the phosphorylation of JNK/p38/ERK proteins was enhanced in the exercise group. These results suggest that exercise stress-induced neuronal inflammatory responses in the hippocampus are associated with HIE-induced cognitive deficits, which may be involved in the upregulation of the JNK/p38/ERK pathway. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.|School of PE, Taiyuan University of Technology, Taiyuan, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Sun
authors.affiliation: School of PE, Taiyuan University of Technology, Taiyuan, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Li
authors.affiliation: School of PE, Taiyuan University of Technology, Taiyuan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Wang
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Mei-Na
authors.initials: MN
authors.lastname: Wu
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of Physiology, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, China.
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D005080:Exercise Test / Q000009:adverse effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology*; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008840:Microfilament Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000009:adverse effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D012333:RNA, Messenger; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases
keywords: JNK/p38/ERK; Y-maze; astrocyte; high-intensity treadmill running; inflammation; long-term potentiation; microglia