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...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.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.21877060 and 31900824)the Postdoctoral Research Foundation of China(No.2019M651779).
文摘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.
