Search

Pathological changes in the medial prefrontal cortex (mPFC) and astrocytes are closely associated with Alzheimer's disease (AD). Voluntary running has been found to effectively delay AD. However, the effects of voluntary running on mPFC astrocytes in AD are unclear. A total of 40 10‐month‐old male amyloid precursor protein/presenilin 1 (APP/PS1) mice and 40 wild‐type (WT) mice were randomly divided into control and running groups, and the running groups underwent voluntary running for 3 months. Mouse cognition was assessed by the novel object recognition (NOR), Morris water maze (MWM), and Y maze tests. The effects of voluntary running on mPFC astrocytes were investigated using immunohistochemistry, immunofluorescence, western blotting, and stereology. APP/PS1 mice performed significantly worse than WT mice in the NOR, MWM, and Y maze tests, and voluntary running improved the performance of APP/PS1 mice in these tests. The total number of mPFC astrocytes was increased, cell bodies were enlarged, and protrusion number and length were increased in AD mice compared with WT mice, but there was no difference in component 3 (C3) levels in the mPFC (total mPFC level); however, C3 and S100B levels in astrocytes were increased in AD mice. Voluntary running reduced the total number of astrocytes and S100B levels in astrocytes and increased the density of PSD95+ puncta in direct contact with astrocyte protrusions in the APP/PS1 mouse mPFC. Three months of voluntary running inhibited astrocyte hyperplasia and S100B expression in astrocytes, increased the density of synapses in contact with astrocytes, and improved cognitive function in APP/PS1 mice. [ABSTRACT FROM AUTHOR]

Leucine‐rich repeat and immunoglobulin‐like domain‐containing nogo receptor‐interacting protein 1 (LINGO‐1), a negative regulator of oligodendrocyte differentiation and myelination, is associated with cognitive function, and its expression is highly upregulated in Alzheimer's disease (AD) patients. Anti‐LINGO‐1 antibody treatment can effectively antagonize the negative regulatory effect of LINGO‐1. In this study, we aim to assess the effect of anti‐LINGO‐1 antibody treatment on cognition and hippocampal oligodendrocytes in an AD transgenic animal model. First, 10‐month‐old male amyloid‐β (Aβ) protein precursor (APP)/presenilin 1 (PS1) mice were administered anti‐LINGO‐1 antibody for 8 weeks. Then, learning and memory abilities were assessed with the Morris water maze (MWM) and Y‐maze tests, and Aβ deposition and hippocampal oligodendrocytes were investigated by immunohistochemistry, immunofluorescence, and stereology. We found that anti‐LINGO‐1 antibody alleviated the deficits in spatial learning and memory abilities and working and reference memory abilities, decreased the density of LINGO‐1 positive cells, decreased Aβ deposition, significantly increased the number of mature oligodendrocytes and the density of myelin, reversed the abnormal increases in the number of oligodendrocyte lineage cells and the densities of oligodendrocytes precursor cells in APP/PS1 mice. Our results provide evidence that LINGO‐1 might be involved in the process of oligodendrocyte dysmaturity in the hippocampus of AD mice, and that antagonizing LINGO‐1 can alleviate cognitive deficits in APP/PS1 mice and decrease Aβ deposition and promote oligodendrocyte differentiation and maturation in the hippocampus of these mice. Our findings suggest that changes in LINGO‐1 and oligodendrocytes in the hippocampus play important roles in the pathogenesis of AD and that antagonizing LINGO‐1 might be a potential therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]