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Canna~Fangled Abstracts

Cannabidiol ameliorates cognitive decline in 5×FAD mouse model of Alzheimer’s disease through potentiating the function of extrasynaptic glycine receptors

By October 12, 2024October 15th, 2024No Comments

. 2024 Oct 12.

doi: 10.1038/s41380-024-02789-x.

Online ahead of print.
Jin Jin # 1, Chonglei Fu # 2 3, Jing Xia # 1, Heyi Luo # 1, Xianglian Wang 1, Si Chen 2, Huanhuan Mao 1, Kai Yuan 4, Lin Lu 5 6 7, Wei Xiong 8 9 10 11, Guichang Zou 12 13
Affiliations 

Abstract

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.

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References

    1. Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056.
    1. Scheltens P. Responding to responsive behaviour in Alzheimer’s disease reply. Lancet. 2021;398:842–842. – PubMed – DOI
    1. Gaugler J, James B, Johnson T, Reimer J, Solis M, Weuve J, et al. 2022 Alzheimer’s disease facts and figures. Alzheimers Dement. 2022;18:700–89. – DOI
    1. Sadick JS, O’Dea MR, Hasel P, Dykstra T, Faustin A, Liddelow SA. Astrocytes and oligodendrocytes undergo subtype-specific transcriptional changes in Alzheimer’s disease. Neuron. 2022;110:1788–+. – PubMed – PMC – DOI
    1. Crimins JL, Rocher AB, Luebke JI. Electrophysiological changes precede morphological changes to frontal cortical pyramidal neurons in the rTg4510 mouse model of progressive tauopathy. Acta Neuropathologica. 2012;124:777–95. – PubMed – PMC – DOI

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