Qiu Dan, Zhou Shi, Donnelly James, Xia Dongdong, Zhao Li
Baotou Teachers' College, Inner Mongolia University of Science and Technology, Baotou 014030, China; Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, China; Physical Activity, Sport and Exercise Research Theme, Faculty of Health, Southern Cross University, Lismore, NSW, Australia.
Physical Activity, Sport and Exercise Research Theme, Faculty of Health, Southern Cross University, Lismore, NSW, Australia.
Exp Gerontol. 2023 Oct 15;182:112293. doi: 10.1016/j.exger.2023.112293. Epub 2023 Sep 22.
Pathological features of Alzheimer's Disease (AD) include alterations in the structure and function of neurons as well as of myelin sheaths. Accumulated evidence shows that aerobic type of exercise can enhance neuroplasticity in mouse models of AD. However, whether and how aerobic exercise can affect myelin sheath repair and neuroprotection in the AD models remains unclear. In this study we tested the hypotheses that 1) myelin structural alterations in 3xTg-AD mice would be related to abnormalities in oligodendrocyte lineage cells, resulting in impaired learning and memory, and 2) a 6-month aerobic exercise intervention would have beneficial effects on such alterations. Two-month-old male 3xTg-AD mice were randomly assigned to a control (AC) or an exercise (AE) group, and age-matched male C57BL/6;129 mice were also randomly assigned to a normal control (NC) or an exercise (NE) group, with n = 12 in each group. Mice in the exercise groups were trained on a motor-drive treadmill, 60 min per day, 5 days per week for 6 months. Cognitive function was assessed at the end of the intervention period. Then, brain specimens were obtained for assessments of morphological and oligodendrocyte lineage cell changes. The results of electron microscopy showed that myelin ultrastructure demonstrated a higher percentage of loose and granulated myelin sheath around axons in the temporal lobe in the AC, as compared with the NC group, along with greater cognitive dysfunction at 8-months of age. These differences were accompanied by significantly greater myelin basic protein (MBP) expression and less neuron-glial antigen-2 (NG2) protein and mRNA levels in the AC, compared to the NC. However, there were no significant between-group differences in the G-ratio (the ratio of axon diameter to axon plus myelin sheath diameter) and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) protein and mRNA levels. The aerobic exercise ameliorated cognitive deterioration and appeared to keep components of myelin sheath and oligodendrocyte precursor cells stabilized, resulting in a decrease in the percentage of loose and granulated myelin sheath and MBP protein, and an increase in NG2 protein and mRNA levels in the AE group. Therefore, the 6-month exercise intervention demonstrated beneficial effects on myelin lesions, abnormal differentiation of oligodendrocytes and general brain function in the 3xTg-AD mice, providing further insights into the role of aerobic exercise in management of neurodegeneration in AD by maintaining intact myelination.
阿尔茨海默病（AD）的病理特征包括神经元以及髓鞘的结构和功能改变。越来越多的证据表明，有氧运动可以增强AD小鼠模型的神经可塑性。然而，有氧运动是否以及如何影响AD模型中的髓鞘修复和神经保护仍不清楚。在本研究中，我们检验了以下假设：1）3xTg-AD小鼠的髓鞘结构改变与少突胶质细胞谱系细胞的异常有关，导致学习和记忆受损；2）为期6个月的有氧运动干预将对这些改变产生有益影响。将2月龄雄性3xTg-AD小鼠随机分为对照组（AC）或运动组（AE），年龄匹配的雄性C57BL/6;129小鼠也随机分为正常对照组（NC）或运动组（NE），每组n = 12。运动组的小鼠在电动跑步机上进行训练，每天60分钟，每周5天，持续6个月。在干预期结束时评估认知功能。然后，获取脑标本以评估形态学和少突胶质细胞谱系细胞变化。电子显微镜结果显示，与NC组相比，AC组颞叶轴突周围髓鞘超微结构显示松散和颗粒状髓鞘的百分比更高，并且在8月龄时伴有更严重的认知功能障碍。与NC组相比，这些差异伴随着AC组中髓鞘碱性蛋白（MBP）表达显著增加，神经元胶质抗原2（NG2）蛋白和mRNA水平降低。然而，在G比率（轴突直径与轴突加髓鞘直径的比率）以及2',3'-环核苷酸3'-磷酸二酯酶（CNPase）蛋白和mRNA水平上，组间没有显著差异。有氧运动改善了认知衰退，似乎使髓鞘和少突胶质前体细胞的成分保持稳定，导致AE组中松散和颗粒状髓鞘以及MBP蛋白的百分比降低，NG2蛋白和mRNA水平升高。因此，为期6个月的运动干预对3xTg-AD小鼠的髓鞘损伤、少突胶质细胞异常分化和整体脑功能显示出有益影响，通过维持完整的髓鞘形成，为有氧运动在AD神经退行性变管理中的作用提供了进一步的见解。
