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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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Categories: 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 7

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Effects of chronic HU210 on neuronal survival. (A) Both naive control ra...
Effects of chronic HU210 on neuronal survival. (A) Both naive control rats and rats receiving twice-daily injections of HU210 (100 μg/kg) for 10 days showed similar density of NeuN-stained neurons in the dentate granule cell layer and CA3 pyramidal cell layer. (B) There was no significant difference in the total number of NeuN-stained cells in the dentate granule cell layer and CA3 pyramidal layer between naive and HU210-treated rats (n = 3 for each group). (C) While naive rats and chronic HU210-treated rats showed no TUNEL-stained cells in the hippocampus, kainic acid–treated (KA-treated) rats exhibited numerous TUNEL-positive neurons in the CA3 pyramidal cell layer and dentate granule cell layer. (D) While naive rats and chronic HU210-treated rats showed no Fluoro-Jade B–stained (FJB-stained) cells in the hippocampus, kainic acid–treated rats exhibited numerous Fluoro-Jade B–positive neurons in the CA3 pyramidal cell layer (n = 3 for each group). Scale bar, 60 μm.
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