1. Anti-LINGO-1 antibody protects neurons and synapses in the medial prefrontal cortex of APP/PS1 transgenic mice.
- Author
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Zhou, Yu-Ning, Jiang, Lin, Zhang, Yi, Zhou, Chun-Ni, Yang, Hao, He, Qi, Wang, Yi-Ying, Xiao, Qian, Huang, Du-Juan, Luo, Yan-Min, Tang, Yong, and Chao, Feng-Lei
- Subjects
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DENDRITIC spines , *TRANSGENIC mice , *PREFRONTAL cortex , *NEURONS , *SYNAPSES , *CENTRAL nervous system - Abstract
The medial prefrontal cortex (mPFC), one of the most vulnerable brain regions in Alzheimer's disease (AD), plays a critical role in cognition. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein-1 (LINGO-1) negatively affects nerve growth in the central nervous system; however, its role in the pathological damage to the mPFC remains to be studied in AD. In this study, an anti-LINGO-1 antibody was administered to 10-month-old APP/PS1 mice, and behavioral tests, stereological methods, immunohistochemistry and immunofluorescence were used to answer this question. Our results revealed that LINGO-1 was highly expressed in the neurons of the mPFC of AD mice, and the anti-LINGO-1 antibody improved prefrontal cortex-related function and reduced the protein level of LINGO-1, atrophy of the volume, Aβ deposition and massive losses of synapses and neurons in the mPFC of AD mice. Antagonizing LINGO-1 could effectively alleviate the pathological damage in the mPFC of AD mice, which might be an important structural basis for improving prefrontal cortex-related function. Abnormal expression of LINGO-1 in the mPFC may be one of the key targets of AD, and the effect initiated by the anti-LINGO-1 antibody may provide an important basis in the search for drugs for the prevention and treatment of AD. • Anti-LINGO-1 antibody delays atrophy of the mPFC and reduces Aβ deposition in the mPFC in AD mice. • Anti-LINGO-1 antibody decreases the neuronal LINGO-1 protein in the mPFC of AD mice. • Anti-LINGO-1 antibody delays the losses of neurons and dendritic spines in the mPFC of AD mice. • Anti-LINGO-1 antibody increases the synapses on the neurite in the mPFC of AD mice. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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