Anti‐LINGO‐1 antibody treatment alleviates cognitive deficits and promotes maturation of oligodendrocytes in the hippocampus of APP/PS1 mice. Issue 10 (27th January 2022)

• Record Type: Journal Article
• Authors: Yang, Hao; Jiang, Lin; Zhang, Yi; Liang, Xin; Tang, Jing; He, Qi; Luo, Yan‐Min; Zhou, Chun‐Ni; Zhu, Lin; Zhang, Shan‐Shan; Xiao, Kai; Zhu, Pei‐Lin; Wang, Jin; Li, Yue; Chao, Feng‐Lei; Tang, Yong
• Is Part Of: Journal of comparative neurology. Volume 530:Issue 10(2022)
• Page Start: 1606
• Page End: 1621
• Publication Date: 2022-01-27
• Subjects: Alzheimer's disease -- anti‐LINGO‐1 antibody -- cognitive abilities -- hippocampus -- oligodendrocytes; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.25299
• Languages: English
• ISSNs: 0021-9967

Abstract

Abstract: 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 : Anti‐LINGO‐1 antibody could improve the behavioral performance of APP/PS1 mice in Morris water maze and Y‐maze. The positive effects of anti‐LINGO‐1 antibody on the cognition of APP/PS1 mice might be related to the anti‐LINGO‐1 antibody‐induced promotion of the differentiation, maturation, and myelination of oligodendrocytes in the hippocampus. The results indicated that LINGO‐1 might be a promising target in the treatment of Alzheimer's disease.