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Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects
Wen Jiang, … , Guang Bai, Xia Zhang
Wen Jiang, … , Guang Bai, Xia Zhang
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3104-3116. https://doi.org/10.1172/JCI25509.
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Research Article Neuroscience

Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects

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Abstract

The hippocampal dentate gyrus in the adult mammalian brain contains neural stem/progenitor cells (NS/PCs) capable of generating new neurons, i.e., neurogenesis. Most drugs of abuse examined to date decrease adult hippocampal neurogenesis, but the effects of cannabis (marijuana or cannabinoids) on hippocampal neurogenesis remain unknown. This study aimed at investigating the potential regulatory capacity of the potent synthetic cannabinoid HU210 on hippocampal neurogenesis and its possible correlation with behavioral change. We show that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, Gi/o proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.

Authors

Wen Jiang, Yun Zhang, Lan Xiao, Jamie Van Cleemput, Shao-Ping Ji, Guang Bai, Xia Zhang

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Figure 4

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Effects of HU210 and AEA on neuronal differentiation of cultured hippoca...
Effects of HU210 and AEA on neuronal differentiation of cultured hippocampal NS/PCs. (A) Incubation of NS/PCs with the culture medium containing either vehicle or 100 nM of HU210 without growth factors for 8 days produced similar density of neurons (pink cells) stained with TuJ1 antibody. The total cultured cells are labeled deep blue by Hoechst staining. (B) There was no significant difference in the ratio of TuJ1-labeled neurons to total cells following application of HU210 (10 nM to 1 μM) or AEA (1 or 5 μM) to culture medium.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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