2. Academic Validation
  3. Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation

Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation

  • Front Med. 2022 Apr;16(2):227-239. doi: 10.1007/s11684-021-0896-8.
Ming Hou 1,  Suji Wang 1,  Dandan Yu 1,  Xinyi Lu 1,  Xiansen Zhao 1,  Zhangpeng Chen 2 3 4,  Chao Yan 5 6 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China. xiaopengczp@163.com.
  • 3 Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, China. xiaopengczp@163.com.
  • 4 Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, 210023, China. xiaopengczp@163.com.
  • 5 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, China. yanchao@nju.edu.cn.
  • 6 Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, China. yanchao@nju.edu.cn.
  • 7 Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, 210023, China. yanchao@nju.edu.cn.
  • 8 Engineering Research Center of Protein and Peptide Medicine, Ministry of Education, Nanjing, 210023, China. yanchao@nju.edu.cn.
PMID: 35212887 DOI: 10.1007/s11684-021-0896-8
Abstract

Chronic stress impairs radial neural stem cell (rNSC) differentiation and adult hippocampal neurogenesis (AHN), whereas promoting AHN can increase stress resilience against depression. Therefore, investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs. The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against depression. However, whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown. Here, by using the chronic restraint stress (CRS) mouse model, we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions. Moreover, transcriptome analysis revealed that the FOXO signaling pathway was involved in the regulation of this process. The administration of CBD rescued depressive-like symptoms in CRS mice and prevented rNSCs overactivation and differentiation into astrocyte, which was partly mediated by the modulation of the FOXO signaling pathway. These results revealed a previously unknown neural mechanism for neural differentiation and AHN in depression and provided mechanistic insights into the antidepressive effects of CBD.

Keywords

cannabidiol; depression; neurogenesis; radial neural stem cells.

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