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Background:Emerging data have demonstrated that peroxisome proliferator-activated receptor δ (PPARδ) activation confers a potentially neuroprotective role in some neurodegenerative diseases. However, whether PPARδ is involved in depression is unknown.Methods:In this study, PPARδ was firstly investigated in the chronic mild stress (CMS) and learned helplessness (LH) models of depression. The changes in depressive behaviors and hippocampal neurogenesis were investigated after PPARδ overexpression by microinfusion of the lentiviral vector, containing the coding sequence of mouse PPARδ (LV-PPARδ), into the bilateral dentate gyri of the hippocampus or PPARδ activation by repeated systemic administration of PPARδ agonist GW0742 (5 or 10mg/kg.d, i.p., for 21 d).Results:We found that both CMS and LH resulted in a significant decrease in the PPARδ expression in the hippocampi of mice, and this change was reversed by treatment with the antidepressant fluoxetine. PPARδ overexpression and PPARδ activation each suppressed the CMS- and LH-induced depressive-like behavior and produced an antidepressive effect. In vivo or in vitro studies also showed that both overexpression and activation of PPARδ enhanced proliferation or differentiation of neural stem cells in the hippocampi of mice.Conclusions:These results suggest that hippocampal PPARδ upregulation represses stress-induced depressive behaviors, accompanied by enhancement of neurogenesis.

Background Although depression is the leading cause of disability worldwide, its pathophysiology is poorly understood. Our previous study showed that hippocampal peroxisome proliferator-activated receptor δ (PPARδ) overexpression displays antidepressive effect and enhances hippocampal neurogenesis during chronic stress. Herein, we further extended our curiosity to investigate whether downregulating PPARδ could cause depressive-like behaviors through downregulation of neurogenesis. Methods Stereotaxic injection of lentiviral vector, expressing short hairpin RNA complementary to the coding exon of PPARδ, was done into the bilateral dentate gyri of the hippocampus, and the depression-like behaviors were observed in mice. Additionally, hippocampal neurogenesis, brain-derived neurotrophic factor and cAMP response element-binding protein were measured both in vivo and in vitro. Results Hippocampal PPARδ knockdown caused depressive-like behaviors and significantly decreased neurogenesis, neuronal differentiation, levels of mature brain-derived neurotrophic factor and phosphorylated cAMP response element-binding protein in the hippocampus. In vitro study further confirmed that PPARδ knockdown could inhibit proliferation and differentiation of neural stem cells. Furthermore, these effects were mimicked by repeated systemic administration of a PPARδ antagonist, GSK0660 (1 or 3 mg/kg i.p. for 21 d). Conclusions These findings suggest that downregulation of hippocampal PPARδ is associated with depressive behaviors in mice through an inhibitory effect on cAMP response element-binding protein/brain-derived neurotrophic factor-mediated adult neurogenesis in the hippocampus, providing new insights into the pathogenesis of depression.

To explore the effect of nerve growth factor on neurons by establishing the animal model of spinal cord injury is the main objective. 40 Sprague Dawley rats were stochasticly divided into a model group and a control group of 20 rats. 5 rats in the model group were selected as model group A and the rest were model group B and 5 rats in the control group were selected as control group A and the rest were control group B. Model group A and control group A were treated with tail vein injection of nerve growth factor. The expression of nerve growth factor, vascular endothelial growth factor, glial fibrillary acidic protein and motor function in groups were observed, to observe the effect of nerve growth factor on proliferation and apoptosis of neuron cells. The expression of nerve growth factor in model group was significantly lower than that in control group (p<0.05) and the expression of nerve growth factor in model group A and control group A was higher than that in model group B and control group B group, respectively (p<0.05). Basso, Beattie and Bresnahan score in model group was lower than that in model group A (p<0.05). The expression of glial fibrillary acidic protein and vascular endothelial growth factor in model group A was higher than that of model group (p<0.05). The proliferation ability of control group was significantly higher than that of model group (p<0.05), the apoptosis rate of model group was higher than control group (p<0.05). Nerve growth factor participates in the occurrence and development of spinal cord injury and is bound up with the proliferation and apoptosis of neuronal cells.