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

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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Effects of the cannabinoid HU210 on PI3K/Akt and ERK signaling in cultur...
Effects of the cannabinoid HU210 on PI3K/Akt and ERK signaling in cultured hippocampal NS/PCs. (A) There was no significant change in pAkt or actin in NS/PCs within the first hour after addition of 100 nM of HU210 to culture medium. (B) Application of 100 nM of HU210 rapidly induced phosphorylation of pERK1/2 in NS/PCs in the presence of bFGF and EGF in culture medium. (C) Application of 100 nM of HU210 3 hours after removal of bFGF and EGF from culture medium also induced phosphorylation of pERK1/2 in NS/PCs. (D) Application of the ERK signaling inhibitor U0126 blocked the promoting effects of 100 nM of HU210 on phosphorylation of pERK1/2 in NS/PCs 5 minutes after addition of HU210 to culture medium. (E) Addition of U0126 (10 μM) to the culture medium 1 hour before HU210 antagonized the promoting effects of 10 nM to 1 μM of HU210 on NS/PC proliferation. Error bars represent SEM. *P < 0.05 and **P < 0.01 by Tukey post-hoc tests after 1-way ANOVA. tERK1/2, total ERK1/2.