Aerobic exercise training decreases cognitive impairment caused by demyelination by regulating ROCK signaling pathway in aging mice

• Published in: Brain research bulletin Vol. 168; pp. 52 - 62
• Main Authors: Bao, Chuncha, He, Chengqi, Shu, Bin, Meng, Tao, Cai, Qiyan, Li, Baichuan, Wu, Guangyan, Wu, Bin, Li, Hongli
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2021
• Subjects: Aerobic exercise training; Aging; Aging - physiology; Animals; Apoptosis; Cognition and memory; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - physiopathology; Corpus Callosum - metabolism; Demyelinating Diseases - metabolism; Demyelination; Male; Mice; Mice, Inbred C57BL; Myelin Sheath - metabolism; Physical Conditioning, Animal - physiology; ROCK signal pathway; Signal Transduction - physiology; MWM; ROCK; LFB; CNS; YC; Aerobic exercise training; PVDF; ROCK signal pathway; NOR; Vehicle; BSA; OC; OD; Demyelination; OE; Aging; Cognition and memory; TEM; ATF3; Apoptosis
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2020.12.010

•Aging may induce memory and cognitive impairment in brain tissue.•The expression of MBP and the thickness of myelin sheath decreased in aged brain.•Aerobic exercise training delays demyelination and impairment of learning and memory.•Apoptosis and myelination are related to the down-regulation of ROCK signal pathway.•Aerobic exercise training could reduce apoptosis and promote regeneration in the CC regions. Recent studies have discovered a strong link between physical exercise and the prevention of neuro-degenerative symptoms, especially in elderly subjects, nonetheless, the exact underlying mechanism remains unclear. In this study, we hypothesized that aerobic exercise training may have a protective effect on myelin sheath in aged mice by regulating the ROCK signal pathway, which is considered as a crucial mechanism for decreasing apoptosis and promoting regeneration. Briefly, C57/BL aged mice underwent an exercise training (5 days/week, lasting 6 weeks). Memory and cognitive impairment were examined using Novel object recognition (NOR) test and Morris water maze test (MWM). Demyelination was explored using Luxol fast blue staining and transmission electron microscopy in the corpus callosum (CC), and the expression of ROCK and apoptotic protein were analyzed via western blot. We demonstrated the impairment of memory and cognitive and the decrease of myelin sheath thickness in aged mice. In addition, severe demyelination was observed in aged mice, accompanied with increased expression of RhoA, ROCK, ATF3, and Caspase 3, and reduced expression of MBP, Olig2, and NG2. Aerobic exercise training improved behavioral functions, increased the expression of MBP and myelin sheath thickness, reduced apoptosis and promoted myelination. To sum up, our data indicate that aerobic exercise training protects demyelination from aging-related white matter injury, which is associated with the up-regulation of ROCK signal pathway.