Anti‐LINGO‐1 antibody treatment alleviates cognitive deficits and promotes maturation of oligodendrocytes in the hippocampus of APP/PS1 mice
- 11 January 2022
- journal article
- research article
- Published by Wiley in Journal of Comparative Neurology
- Vol. 530 (10), 1606-1621
- https://doi.org/10.1002/cne.25299
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 APP/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 amyloid-beta (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. This article is protected by copyright. All rights reservedKeywords
Funding Information
- National Natural Science Foundation of China (81801269, 81871073, 82002227)
This publication has 66 references indexed in Scilit:
- Oligodendroglia metabolically support axons and contribute to neurodegenerationNature, 2012
- Hippocampal expression of myelin‐associated inhibitors is induced with age‐related cognitive decline and correlates with deficits of spatial learning and memoryJournal of Neurochemistry, 2012
- An Alzheimer's disease‐relevant presenilin‐1 mutation augments amyloid‐beta‐induced oligodendrocyte dysfunctionGlia, 2011
- Longitudinal Changes in White Matter Disease and Cognition in the First Year of the Alzheimer Disease Neuroimaging InitiativeArchives of Neurology, 2010
- Oligodendrocytes Changing the Rules: Action Potentials in Glia and Oligodendrocytes Controlling Action PotentialsThe Neuroscientist, 2008
- White matter in learning, cognition and psychiatric disordersTrends in Neurosciences, 2008
- Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease modelsProceedings of the National Academy of Sciences of the United States of America, 2007
- Morris water maze: procedures for assessing spatial and related forms of learning and memoryNature Protocols, 2006
- Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer’s diseaseProceedings of the National Academy of Sciences of the United States of America, 2006
- Effect of Morris water maze diameter on visual-spatial learning in different mouse strainsNeurobiology of Learning and Memory, 2006