Jin Jin, Chonglei Fu, Jing Xia, Heyi Luo, Xianglian Wang, Si Chen, Huanhuan Mao, Kai Yuan, Lin Lu, Wei Xiong, Guichang Zou
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Cannabidiol ameliorates cognitive decline in 5×FAD mouse model of Alzheimer’s disease through potentiating the function of extrasynaptic glycine receptors
Emerging evidence supports the therapeutic potential of cannabinoids in Alzheimer’s disease (AD), but the underlying mechanism upon how cannabinoids impact brain cognition and AD pathology remains unclear. Here we show that chronic cannabidiol (CBD) administration significantly mitigates cognitive deficiency and hippocampal β-amyloid (Aβ) pathology in 5×FAD mouse model of AD. CBD achieves its curative effect mainly through potentiating the function of inhibitory extrasynaptic glycine receptor (GlyR) in hippocampal dentate gyrus (DG). Based on the in vitro and in vivo electrophysiological recording and calcium imaging, CBD mediated anti-AD effects via GlyR are mainly accomplished by decreasing neuronal hyperactivity of granule cells in the DG of AD mice. Furthermore, the AAV-mediated ablation of DG GlyRα1, or the GlyRα1S296A mutation that exclusively disrupts CBD binding, significantly intercepts the anti-AD effect of CBD. These findings suggest a GlyR dependent mechanism underlying the therapeutic potential of CBD in the treatment of AD.
期刊介绍：
Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.
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