Research Paper Volume 15, Issue 6 pp 2158—2169
Reduction of NgR in perforant path protects neuronal morphology and function in APP/PS1 transgenic mice
- 1 Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, China
- 2 Department of Physiology, Binzhou Medical University, Yantai Campus, Yantai, China
- 3 Department of Neurology, Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian, China
- 4 Department of Traumatic Orthopedics, Yantaishan Hospital, Yantai, China
Received: December 16, 2021 Accepted: March 23, 2022 Published: March 23, 2023
https://doi.org/10.18632/aging.204605How to Cite
Copyright: © 2023 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Neuronal loss is the central abnormality occurring in brains suffering from Alzheimer’s disease (AD). The notion that AD causes the death of neurons point towards protection of neuronal morphology and function as important therapeutic strategies. The perforant path projections from the entorhinal cortex to the dentate gyrus is the most vulnerable circuit with respect to AD. It’s known that the perforant path is a very important structure for synaptic plasticity and cognitive functions. NgR (Nogo receptor) is not only involved in limiting injury-induced axonal growth but also in pathological features of AD. So, the mechanism of how NgR affects the perforant path needs further investigation. In this study, the effect of NgR in the perforant path on the neuronal morphology and function in APP/PS1 transgenic mice was studied. The results showed that downregulation of NgR in perforant path ameliorate the damaged morphology and decreased number of neurons in APP/PS1 mice. Concurrently, NgR knockdown enhanced dendritic complexity and increased postsynaptic protein density in APP/PS1 mice. Furthermore, the RT-PCR results indicated that there is downregulation of M1 phenotypes of microglial gene expression in the hippocampus of TG-shNgR mice. Our study suggests that NgR plays a critical role in microglial phenotype polarization, which might account for the NgR knockdown in the perforant path initiated a decrease in neuronal death and improved synaptic function. Our study provided a better understanding of the perforant path and the role of NgR in AD pathogenesis, thus offering the potential application of hippocampal neurons in treatment of AD.