Effects of running on medial prefrontal cortex and microglia in APP/PS1 mice

Abstract

Objective To investigate the effects of running on the volume change of medial prefrontal cortex (mPFC), as well as amyloid beta protein (Aβ) and microglia in mPFC in mouse model of Alzheimer′s disease (AD). Methods Male APP/PS1 transgenic AD mice aged 10 months were randomly divided into AD running group (AD Run, given active running intervention for 4 months) and AD control group (AD Ctrl), while non-transgenic mice at the same age were set as normal control group (Ctrl). The mice from the AD Ctrl and Ctrl groups received no treatment. Morris water maze test was used to evaluate the abilities of spatial learning and memory of mice, and Y maze test was adopted to assess the working memory and reference memory in the mice. The volume of mPFC and the total number of microglia (IBA1+cells) in the mPFC were quantified with stereological methods. The number of activated microglia (CD68+/IBA1+ cells) in the mPFC, cell body area, and process number of microglia, number and area of Aβ plaques, and area of Aβ plaques in IBA1+ microglia were quantitatively measured by immunofluorescence multiple labeling and laser confocal microscopy, and the ratio of area of Aβ plaques in IBA1+ microglia to the total area of Aβ plaques was calculated. Results The AD Run group and Ctrl group performed better than the AD Ctrl group in Morris water maze and Y maze tests. The volume of mPFC was significantly less in the AD Ctrl group than the Ctrl group (P < 0.05), while that of the AD Run group was obviously larger than that of the AD Ctrl (P < 0.01). The AD Ctrl group had greatly larger numbers of IBA1+ cells and CD68+/IBA1+ cells in the mPFC than the Ctrl group (P < 0.05), whereas the AD Run group had much larger numbers of those cells than the AD Ctrl group (P < 0.05). The total and average area of Aβ plaques in the mPFC was greatly diminished in the AD Run group than the AD Ctrl group (P < 0.05). In addition, the AD Run group also presented larger numbers of IBA1+ cells and CD68+/IBA1+ cells around Aβ, larger average body area of single microglia and CD68+/IBA1+ cells, and elevated area of Aβ plaques in IBA1+ cells, along with its ratio to the total area of Aβ plaques in mPFC improved (P < 0.05). Conclusion Running exercise increases the number of CD68+ microglia in the mPFC, reduces the Aβ plaques, delays the atrophy of mPFC, and thus improves the spatial learning and memory abilities as well as working memory and reference memory in APP/PS1 transgenic AD mice.

Keywords

• alzheimer′s disease
• running
• medial prefrontal cortex
• microglia
• cd68
• aβ