Protective effect of aerobic exercise on myelin lesions in an AD model and its mechanism

Dan Qiu

doi:10.25918/thesis.420

Research background and questions: Alzheimer's Disease (AD) is a common age-related neurodegenerative disease. Previous studies have found abnormal changes in myelin sheath of AD. Myelin sheath is a multi-layer glial membrane surrounding axons, which is produced by oligodendrocytes in the central nervous system. The Akt-mTOR signalling pathway is found to be closely related to proliferation and differentiation of oligodendrocytes. This thesis employed a 3×Tg-AD mouse model to examine: 1) whether an aerobic exercise intervention could affect the morphology and/or function of myelin sheath and oligodendrocytes, and 2) whether the effects of exercise on myelin in AD were related to the Akt-mTOR signalling pathway. Methodology: The subjects were two-month-old, male APP/PS1/tau transgenic (3×Tg-AD) mice and non-transgenic control mice of the same mixed B6129SF2 background. The respective mice were randomly divided into an AD control group (AC), AD exercise group (AE), normal control group (NC) and normal exercise group (NE), with n=12 in each group. The AE and NE mice were given a treadmill exercise intervention with 60 min/day, 5 days/week, for six months. Effects of exercise on AD were examined by: 1) the platform avoidance test to evaluate the learning and memory ability, 2) the ultrastructure changes of myelin sheath in the temporal lobe via transmission electron microscopy, 3) the changes in morphology and distribution of myelin basic protein (MBP), and the node of Ranvier labelled protein (Caspr1) using immunofluorescence, 4) the differentiation of oligodendrocytes by the protein expressions of MBP, Caspr1, oligodendrocyte labelled protein (CNPase) and oligodendrocyte precursor labelled protein (NG2) in the temporal lobe using Western Blot; the morphology and distribution of oligodendrocytes and oligodendrocyte precursors estimated using immunofluorescence; and the mRNA of MBP, CNPase and NG2 measured using RT-PCR, and 5) the key proteins of the Akt-mTOR signalling pathway in the temporal lobe measured using Western Blot. Two-way ANOVA was employed to examine these potential effects of AD and exercise intervention and their interactions. Results: (1) The AD model mice showed loose and granulated myelin structure in the temporal lobe together with cognitive dysfunction. The AE group showed a relatively normal structure of myelin sheath and cognitive function. (2) the Caspr1 protein expression level in the AC group was significantly lower than that in the NC group, and that in the AE group was significantly higher than and that in the AC group. (3) The protein expression of MBP in the AC group was higher than the NC group, whilst the protein, mRNA expression, fluorescent staining area and density of NG2 were significantly lower. The aerobic exercise appeared to have the effect of keeping the components of myelin sheath and oligodendrocyte precursor cells stabilized, which was associated with normal differentiation of oligodendrocytes. (4) There were no significant differences in CNPase protein expression, mRNA level, fluorescence staining area, density and intensity among all groups. (5) Hyperphosphorylation of key proteins in the Akt-mTOR signalling pathway was observed in the AC group, whilst the phosphorylation was normal in the AE group. Conclusion: The aerobic exercise appeared to serve a protective role for the myelin lesions, abnormal differentiation of oligodendrocytes in AD via the Akt-mTOR signalling pathway.

Protective effect of aerobic exercise on myelin lesions in an AD model and its mechanism

Files and links (1)

Metrics

Abstract

Details

Protective effect of aerobic exercise on myelin lesions in an AD model and its mechanism

Files and links (1)

Metrics

Abstract

Details

Southern Cross University Social media