Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication.

Autor: Hasegawa Y; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Kim J; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Korea Brain Research Institute, Daegu, Republic of Korea., Ursini G; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Jouroukhin Y; Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences SUNY, University at Buffalo, Buffalo, NY, USA., Zhu X; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Miyahara Y; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Xiong F; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Madireddy S; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Obayashi M; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Lutz B; Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.; Leibniz Institute for Resilience Research (LIR) gGmbH, Mainz, Germany., Sawa A; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA., Brown SP; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA., Pletnikov MV; Department of Physiology and Biophysics, Jacobs School of Medicine and Biomedical Sciences SUNY, University at Buffalo, Buffalo, NY, USA. mvpletni@buffalo.edu., Kamiya A; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. akamiya1@jhmi.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Oct 25; Vol. 14 (1), pp. 6559. Date of Electronic Publication: 2023 Oct 25.
DOI: 10.1038/s41467-023-42276-5
Abstrakt: Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. However, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, is not fully understood. Here, we report that in mice, adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in a model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings suggest the microglial Cnr1 may contribute to adverse effect of cannabis exposure in genetically vulnerable individuals.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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