Anti-LINGO-1 antibody ameliorates cognitive impairment, promotes adult hippocampal neurogenesis, and increases the abundance of CB1R-rich CCK-GABAergic interneurons in AD mice
| Autor: | Chunni Zhou, Yong Tang, Qian Xiao, Yanmin Luo, Lei Zhang, Jing Tang, Xin Liang, Shan-shan Zhang, Yuhan Xie, Yi Zhang, Qi He, Du-Juan Huang, Lin Jiang, Yu-Hui Deng, Yi-Jing Guo, Hao Yang, Feng-lei Chao, Lin Zhu, Yu-Ning Zhou, Xiao-yun Dou |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Amyloid beta Neurogenesis medicine.medical_treatment Transgene Hippocampus Mice Transgenic Nerve Tissue Proteins Neurosciences. Biological psychiatry. Neuropsychiatry Hippocampal formation Mice 03 medical and health sciences 0302 clinical medicine Receptor Cannabinoid CB1 Alzheimer Disease Interneurons Receptor-Interacting Protein Serine-Threonine Kinase 2 medicine Animals CB1R Cognitive Dysfunction GABAergic Neurons Receptor biology Cognitive abilities Antibodies Monoclonal Membrane Proteins GABAergic interneurons 030104 developmental biology nervous system Neurology AD mice biology.protein Adult hippocampal neurogenesis GABAergic Cannabinoid Neuroscience LINGO-1 030217 neurology & neurosurgery RC321-571 |
| Zdroj: | Neurobiology of Disease, Vol 156, Iss, Pp 105406-(2021) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2021.105406 |
| Popis: | In view of the negative regulatory effect of leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (LINGO-1) on neurons, an antibody against LINGO-1 (anti-LINGO-1 antibody) was herein administered to 10-month-old APP/PS1 transgenic Alzheimer's disease (AD) mice for 2 months as an experimental intervention. Behavioral, stereology, immunohistochemistry and immunofluorescence analyses revealed that the anti-LINGO-1 antibody significantly improved the cognitive abilities, promoted adult hippocampal neurogenesis (AHN), decreased the amyloid beta (Aβ) deposition, enlarged the hippocampal volume, and increased the numbers of total neurons and GABAergic interneurons, including GABAergic and CCK-GABAergic interneurons rich in cannabinoid type 1 receptor (CB1R), in the hippocampus of AD mice. In contrast, this intervention significantly reduced the number of GABAergic interneurons expressing LINGO-1 and CB1R in the hippocampus of AD mice. More importantly, we also found a negative correlation between LINGO-1 and CB1R on GABAergic interneurons in the hippocampus of AD mice, while the anti-LINGO-1 antibody reversed this relationship. These results indicated that LINGO-1 plays an important role in the process of hippocampal neuron loss in AD mice and that antagonizing LINGO-1 can effectively prevent hippocampal neuron loss and promote AHN. The improvement in cognitive abilities may be attributed to the improvement in AHN, and in the numbers of GABAergic interneurons and CCK-GABAergic interneurons rich in CB1Rs in the hippocampus of AD mice induced by the anti-LINGO-1 antibody. Collectively, the double target effect (LINGO-1 and CB1R) initiated by the anti-LINGO-1 antibody may provide an important basis for the study of drugs for the prevention and treatment of AD in the future. |
| Databáze: | OpenAIRE |
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