Our previous study showed that up-regulating hippocampal peroxisome proliferator-activated receptorδ(PPARδ)displays an antidepressive effect and enhanc-es hippocampal neurogenesis in the context of chronic stress.He...Our previous study showed that up-regulating hippocampal peroxisome proliferator-activated receptorδ(PPARδ)displays an antidepressive effect and enhanc-es hippocampal neurogenesis in the context of chronic stress.Here,the changes in depressive behaviors and hippocampal neurogenesis were investigated after PPARδknockdown by microinfusion of the lentiviral vector,expressing short hairpin RNA(sh RNA)complementary to the coding exon of PPARδ,into the bilateral dentate gyri of the hippocampus or PPARδblockade by repeated systemic administration of PPARδantagonist,GSK0660(1 or 3mg·kg-1,ip,for 21 d).We found that hippocampal PPARδknockdown or blockade induced depressive-like behaviors and increased vulnerability to stress,which is involved in decreased hippocampal neurogenesis and neuronal differentiation.Down-regulating hippocampal PPARδalso induced significant decreases in phosphorylation c AMP response element-binding protein(CREB)and BDNF level in the hippocampus.The in vitro study that PPARδknockdown or blockade inhibited proliferation and differentiation of neural stem cells.Taken together,our results suggest that PPARδcould be a novel and promising target for developing new PPARδagonists for the treatment of depressive disorders.展开更多
基金The project supported Natural Science Foundation of Jiangsu Province(SBK201320969)National Natural Science Foundation of China(81573413 and 81273497)
文摘Our previous study showed that up-regulating hippocampal peroxisome proliferator-activated receptorδ(PPARδ)displays an antidepressive effect and enhanc-es hippocampal neurogenesis in the context of chronic stress.Here,the changes in depressive behaviors and hippocampal neurogenesis were investigated after PPARδknockdown by microinfusion of the lentiviral vector,expressing short hairpin RNA(sh RNA)complementary to the coding exon of PPARδ,into the bilateral dentate gyri of the hippocampus or PPARδblockade by repeated systemic administration of PPARδantagonist,GSK0660(1 or 3mg·kg-1,ip,for 21 d).We found that hippocampal PPARδknockdown or blockade induced depressive-like behaviors and increased vulnerability to stress,which is involved in decreased hippocampal neurogenesis and neuronal differentiation.Down-regulating hippocampal PPARδalso induced significant decreases in phosphorylation c AMP response element-binding protein(CREB)and BDNF level in the hippocampus.The in vitro study that PPARδknockdown or blockade inhibited proliferation and differentiation of neural stem cells.Taken together,our results suggest that PPARδcould be a novel and promising target for developing new PPARδagonists for the treatment of depressive disorders.
