Protective effects of exercise on the myelin sheath, glial cells, and cognitive decline in naturally aging rats

WANG Xin, WANG Qi, ZHANG Zhan-bai-ling, LIAO Jing-wen, ZUO Bai-rui, MU Lian-wei

Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (3) : 271-279.

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (3) : 271-279. DOI: 10.16098/j.issn.0529-1356.2026.03.001
Neurbiology

Protective effects of exercise on the myelin sheath, glial cells, and cognitive decline in naturally aging rats

  • WANG  Xin  WANG  Qi  ZHANG  Zhan-bai-ling  LIAO  Jing-wen  ZUO  Bai-rui *  MU Lian-wei*
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Abstract

Objective  To investigate the protective effects of aerobic exercise on the myelin sheath, glial cells, and cognitive decline in naturally aging female rats.  Methods  Three-month-old and 16-month-old rats were selected as the young control group (YC, n=6) and the old control group (OC, n=6), respectively. The old exercise group (OE, n=6) underwent an exercise intervention from 3 to 16 months of age. The novel object recognition test and the Y-maze were used to assess the learning and memory abilities of rats. Immunofluorescent staining measured the levels of myelin sheath and oligodendrocytes(OGD) in the brain tissue of each group, as well as the activation status of microglia(MG) and astrocytes(AS). Western blotting was employed to detect the expression level of the myelin basic protein(MBP) protein.  Results  Naturally aging rats exhibited significant impairments in learning and memory, which could be effectively ameliorated through exercise intervention. The myelin sheath levels in the hippocampal CA3 region and corpus callosum, the MBP levels in the CA3 of aged control rats were significantly lower than those in the young control rats. In contrast, the activation levels of microglia and astrocytes in the hippocampal CA1, CA3, and prefrontal cortex were significantly higher than those in the young controls. Exercise intervention effectively increased myelin levels in the CA3 region of the hippocampus and the corpus callosum, the MBP levels in the CA3 of aged rats, while reducing the activation of microglia and astrocytes in the CA1, CA3, and prefrontal cortex regions of the hippocampus. However, there were no significant differences in oligodendrocyte levels among the young control, old control, and old exercise groups.   Conclusion  Exercise intervention can effectively reduce myelin loss and decrease the activation of microglia and astrocytes. This may be one of the mechanisms by which aerobic exercise improves learning and memory impairments in naturally aging rats.

Key words

Exercise  / Aging  / Myelin sheath  / Oligodendrocyte  / MicrogliaAstrocyte  / Novel object recognition test  / Rat

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WANG Xin, WANG Qi, ZHANG Zhan-bai-ling, LIAO Jing-wen, ZUO Bai-rui, MU Lian-wei. Protective effects of exercise on the myelin sheath, glial cells, and cognitive decline in naturally aging rats[J]. Acta Anatomica Sinica. 2026, 57(3): 271-279 https://doi.org/10.16098/j.issn.0529-1356.2026.03.001

References

[1]Guo X, Wu Y, Wang Y, et al. Prediction of population aging trend and analysis of influencing factors based on grey fractional-order and grey relational models: a case study of Jiangsu Province, China[J]. BMC Geriatr, 2025,25(1):197.
[2] Guerrero-Gonzlez C, Cueto-Urea C, Cantn-Habas V, et al. Healthy aging in menopause: prevention of cognitive decline, depression and dementia through physical exercise[J]. Physiologia, 2024,4(1):115-138.
[3]Xu T, Bu G, Yuan L, et al. The prevalence and risk factors study of cognitive impairment: analysis of the elderly population of Han nationality in Hunan province, China[J]. CNS Neurosci Ther, 2024,30(4):e14478.
[4] Salthouse TA. Trajectories of normal cognitive aging[J]. Psychol Aging, 2019,34(1):17-24.
[5] Henderson VW, Popat RA. Effects of endogenous and exogenous estrogen exposures in midlife and late-life women on episodic memory and executive functions[J]. Neuroscience, 2011,191:129-138.
[6] Luine VN, Richards ST, Wu VY, et al. Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters[J]. Horm Behav, 1998,34(2):149-162.
[7] Frick KM, Fernandez SM, Bulinski SC. Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice[J]. Neuroscience, 2002,115(2):547-558.
[8] Amini R, Chee KH, Swan J, et al. The level of cognitive impairment and likelihood of frequent hospital admissions[J]. J Aging Health, 2019,31(6):967-988.
[9] Dimou L, Simon C, Kirchhoff F, et al. Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex[J]. J Neurosci, 2008,28(41):10434-10442.
[10] Hill RA, Li AM, Grutzendler J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain[J]. Nat Neurosci, 2018,21(5):683-695.
[11] Wang F, Ren SY, Chen JF, et al. Myelin degeneration and diminished myelin renewal contribute to age-related deficits in memory[J]. Nat Neurosci, 2020,23(4):481-486.
[12] Hahn O, Foltz AG, Atkins M, et al. Atlas of the aging mouse brain reveals white matter as vulnerable foci[J]. Cell, 2023,186(19):4117-4133.
[13] Bendlin BB, Fitzgerald ME, Ries ML, et al. White matter in aging and cognition: a cross-sectional study of microstructure in adults aged eighteen to eighty-three[J]. Dev Neuropsychol, 2010,35(3):257-277.
[14] Peter C, Sathe A, Shashikumar N, et al. White matter abnormalities and cognition in aging and Alzheimer’s disease[J]. JAMA Neurol, 2025,82(8):825-836.
[15] Pang Y, Campbell L, Zheng B, et al. Lipopolysaccharide-activated microglia induce death of oligodendrocyte progenitor cells and impede their development[J]. Neuroscience, 2010,166(2):464-475.
[16]Taylor DL, Pirianov G, Holland S, et al. Attenuation of proliferation in oligodendrocyte precursor cells by activated microglia[J]. J Neurosci Res, 2010,88(8):1632-1644.
[17] Yeo YA, Martínez GJ, Croxford JL, et al. CD137 ligand activated microglia induces oligodendrocyte apoptosis via reactive oxygen species[J]. J Neuroinflammation, 2012,9:173.
[18]Hammond TR, Gadea A, Dupree J, et al. Astrocyte-derived endothelin-1 inhibits remyelination through notch activation[J]. Neuron, 2014,81(3):588-602.
[19] Jiang J, Sun Y, Ma Y, et al. Advances in therapeutics research for demyelinating diseases[J]. Pharmaceuticals (Basel), 2025,18(12):1835.
[20] Yaffe K, Barnes D, Nevitt M, et al. A prospective study of physical activity and cognitive decline in elderly women: women who walk[J]. Arch Intern Med, 2001,161(14):1703-1708.
[21] Iso-Markku P, Kujala UM, Knittle K, et al. Physical activity as a protective factor for dementia and Alzheimer’s disease: systematic review, meta-analysis and quality assessment of cohort and case-control studies[J]. Br J Sports Med, 2022,56(12):701-709.
[22] Mu L, Cai J, Gu B, et al. Treadmill exercise prevents decline in spatial learning and memory in 3×Tg-AD mice through enhancement of structural synaptic plasticity of the hippocampus and prefrontal cortex[J]. Cells, 2022,11(2):244.
  [23] Ruan S, Liu J, Yuan X, et al. Aerobic exercise alleviates cognitive impairment in T2DM mice through gut microbiota[J]. Sci Rep, 2025,15(1):23917. 
[24] Ren H, Zhang Z, Zhang J. Physical exercise exerts neuroprotective effect on memory impairment by mitigate the decline of striatum catecholamine and spine density in a vascular dementia rat model[J]. Am J Alzheimers Dis Other Demen, 2022,37: 15333175221144367.
[25] Bao C, He C, Shu B, et al. Aerobic exercise training decreases cognitive impairment caused by demyelination by regulating ROCK signaling pathway in aging mice[J]. Brain Res Bull, 2021,168:52-62.
[26] van Praag H, Shubert T, Zhao C, et al. Exercise enhances learning and hippocampal neurogenesis in aged mice[J]. J Neurosci, 2005,25(38):8680-8685.
 [27] Li PD, Han C, Qin YY, et al. Exercise-induced alleviation of memory impairment in aged mice with neuroinflammation is linked with modulation of mitochondrial homeostasis in the hippocampus[J]. J Gerontol A Biol Sci Med Sci, 2026,81(1):glaf233.
[28] Guo L, Li S, Zhang Y, et al. Effects of exercise intensity on spatial memory performance and hippocampal synaptic function in SAMP8 mice[J]. Neurobiol Learn Mem, 2023,203:107791.
[29] Salthouse TA. When does age-related cognitive decline begin [J]? Neurobiol Aging, 2009,30(4):507-514.
[30] Sharma M, Goswami I. Multivariate decomposition of gender differentials in cognitive impairment among older adults in India based on Longitudinal Ageing Study in India, 2017-2018[J]. BMC Psychiatry,2025,25(1):385.
[31] Shafiei B, Shabani M, Afgar A, et al. Trehalose attenuates learning and memory impairments in aged rats via overexpression of miR-181c[J]. Neurochem Res, 2022,47(11):3309-3317.
[32] Sun D, Gao G, Zhong B, et al. NLRP1 inflammasome involves in learning and memory impairments and neuronal damages during aging process in mice[J]. Behav Brain Funct, 2021,17(1):11.
[33] Yan MS, Shu LJ, Wang ChG, et al. Exercise regulates hippocampal neuronal structural plasticity and neurogenesis to improve memory impairment in high-fat diet-induced obese mice[J]. Progress in Biochemistry and Biophysics, 2025,52(4):995-1007. (in Chinese)
严梦思, 舒麟捷, 王朝格, 等. 运动调控海马神经元结构可塑性和神经发生改善高脂饮食诱导的肥胖小鼠记忆损害[J]. 生物化学与生物物理进展, 2025,52(4):995-1007.
[34]Mu LW, Han P, Yang YJ. Exercise intervention alleviating learning and memory dysfunction of Alzheimer’s disease model mice through modulating autophagy of hippocampal neurons[J]. Acta Anatomica Sinica, 2024, 55(5):533-540.(in Chinese)
牟连伟, 韩鹏, 杨运杰. 运动干预调控海马神经元自噬改善阿尔茨海默病模型小鼠学习记忆障碍[J]. 解剖学报, 2024,55(5):533-540.
[35] Dimovasili C, Fair AE, Garza IR, et al. Aging compromises oligodendrocyte precursor cell maturation and efficient remyelination in the monkey brain[J]. Geroscience, 2023,45(1):249-264.
[36] Langley MR, Choi CI, Peclat TR, et al. Critical role of astrocyte NAD(+) glycohydrolase in myelin injury and regeneration[J]. J Neurosci, 2021,41(41):8644-8667.

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