(Peer-Reviewed) Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation
Ming Hou ¹, Suji Wang ¹, Dandan Yu ¹, Xinyi Lu ¹, Xiansen Zhao ¹, Zhangpeng Chen 陈张鹏 ¹ ² ³, Chao Yan 闫超 ¹ ² ³ ⁴
¹ State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China
中国 南京 南京大学生命科学学院 医药生物技术国家重点实验室
² Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing 210023, China
中国 南京 南京大学人工智能生物医药技术研究院
³ Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210023, China
中国 南京 南京大学化学和生物医药创新研究院
⁴ Engineering Research Center of Protein and Peptide Medicine, Ministry of Education, Nanjing 210023, China
中国 南京 蛋白质与多肽新药教育部工程研究中心
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.
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