Voluntary running exercise promotes maturation differentiation and myelination of oligodendrocytes around Aβ plaques in the medial prefrontal cortex of APP/PS1 mice.

BACKGROUND

Previous studies have reported that running exercise could improves myelinization in hippocampus. However, the effects of running exercise on the differentiation and maturation of oligodendrocytes, and myelination surrounding Aβ plaques in the medial prefrontal cortex (mPFC) of the Alzheimer's disease (AD) brain have not been reported.

METHODS

Forty 10-month-old male APP/PS1 AD mice were randomly divided into the AD group and the AD running (AD+RUN) group, while 20 age-matched wild-type littermate mice were included in the WT group. The running group received three-month voluntary running exercise in a running cage, while the AD and WT groups were untreated. After the exercise intervention, all mice were given behavioral tests. The total number of mature oligodendrocytes (CC1) in the mPFC of mice was precisely quantified using unbiased stereology. Myelin basic protein (MBP) and Aβ plaque, as well as the fluorescence area of MBP surrounding Aβ plaques, and the density and morphology of PDGFα cells in the mPFC were analyzed using immunofluorescence.

RESULTS

The levels of working memory, cognitive memory, spatial learning and memory ability were decreased significantly in the AD group compared to the WT group, while these functions were significantly improved in the AD+RUN group compared to the AD group. The Aβ plaques in the mPFC were significantly reduced in the AD+RUN group compared to the AD group. The total number of CC1 cells and the percentage of MBP fluorescence area surrounding Aβ plaques in the mPFC were significantly lower in the AD group compared to the WT group, but they were significantly higher in the AD+RUN group compared to the AD group. The density and branching complexity of PDGFα cells surrounding Aβ plaques in the mPFC were significantly higher in the AD group than in the WT group, while the AD+RUN group showed significantly lower density and branching complexity than the AD group. Changes in MBP expression around Aβ plaques, cell density and cell branching complexity of PDGFα cells around Aβ plaques were closely related to the number of Aβ plaques in mPFC, and they were also closely related to behavioral changes in mice.

CONCLUSIONS

Voluntary running exercise could reduce Aβ plaque deposition and promote the maturation and myelination capacity of oligodendrocytes surrounding Aβ plaques in the mPFC of AD mice, thereby improving the learning and memory abilities of APP/PS1 transgenic AD mice.