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Research Paper|Volume 14, Issue 8|pp 3554—3568

Claudin-5 relieves cognitive decline in Alzheimer’s disease mice through suppression of inhibitory GABAergic neurotransmission

Ning Zhu1,4, Meidan Wei2, Linguang Yuan3, Xiaodan He1, Chunli Chen4, Aimin Ji4, Guozeng Zhang5
  • 1General Practice Center, The Seventh Affiliated Hospital, Southern Medical University, Foshan 528244, China
  • 2Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China
  • 3College of Basic Medicine, Changsha Medical University, Changsha 410219, China
  • 4Department of Pharmacy, The Seventh Affiliated Hospital, Southern Medical University, Foshan 528244, China
  • 5Institute of Nursing and Health, School of Nursing and Health, Henan University, Kaifeng 475004, China
Received: December 7, 2021Accepted: March 8, 2022Published: April 26, 2022
https://doi.org/10.18632/aging.204029

Copyright: © 2022 Zhu 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

Alzheimer’s disease (AD) is characterized by progressive cognitive decline, which is considered as the most common form of dementia in the elderly. Recently, it is suggested that impaired cerebrovascular function may precede the onset of AD. Claudin-5, which is the most enriched tight junction protein, has been reported to prevent the passage of damaging material at the blood-brain barrier. However, whether claudin-5 impacts AD has no direct evidence. We found a decrease level of claudin-5 in the hippocampus of AD and elder mice. And intravenous injection of claudin-5 improved learning and memory ability in these mice, while knockout of the protein led to impaired learning and memory and long-term potentiation in adult control mice. Furthermore, the effects of claudin-5 are mediated by suppressing inhibitory GABAergic neurotransmission. Our results suggest benefit effects of claudin-5 on learning and memory, which may provide a new treatment strategy for AD.