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

被引:5
作者
Hou, Ming [1 ]
Wang, Suji [1 ]
Yu, Dandan [1 ]
Lu, Xinyi [1 ]
Zhao, Xiansen [1 ]
Chen, Zhangpeng [1 ,2 ,3 ]
Yan, Chao [1 ,2 ,3 ,4 ]
机构
[1] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Peoples R China
[2] Nanjing Univ, Inst Artificial Intelligence Biomed, Nanjing 210023, Peoples R China
[3] Nanjing Univ, Chem & Biomed Innovat Ctr, Nanjing 210023, Peoples R China
[4] Minist Educ, Engn Res Ctr Prot & Peptide Med, Nanjing 210023, Peoples R China
基金
中国国家自然科学基金;
关键词
cannabidiol; depression; radial neural stem cells; neurogenesis; ADULT HIPPOCAMPAL NEUROGENESIS; CHRONICALLY STRESSED MICE; ENDOCANNABINOID SYSTEM; NEUROBIOLOGY; INVOLVEMENT; DEPLETION; RESPONSES; TARGET;
D O I
10.1007/s11684-021-0896-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:227 / 239
页数:13
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