OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts n...OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts neuroprotection after cerebral ischemia.However,whether OEA affects the outcomes of diabetes-induced encephalopathy(DE) requires further study.METHODS The chronic effects of OEA on DE were evaluated in C57BL/6 and PPARαknockout mice,individually.The cognitive function was assessed with Morris water maze.The expression of receptor for advanced glycation end products(RAGE) and phosphorylation of Tau in mice hippocampus were determined using Western blotting.The influence of OEA in neuron loss and neuroplasticity were assessed with immunofluorescent staining and Western blotting.RESULTS OEA markedly ameliorated performance in the Morris water maze,which was correlated with its capabilities of suppressing glycometabolism and phosphorylation of Tau in the hippocampus.OEA offered protection from diabetes-induced impairments in hippocampal neuroplasticity.Furthermore,the changes in Morris water maze performance and neuron loss could not be observed in PPARα knockout mouse models with OEA administration.CONCLUSION The ability of OEA to control PPARα signaling can serve as a novel neuroprotective approach for the treatment of diabetes-induced encephalopathy.展开更多
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Fun-damental Research Funds for the Central Universities (20720180042)Health Science ResearchPersonnel Training Program of Fujian Province(2018-CXB-30)+2 种基金Natural Science Foundation of Fujian, China (2016J014152016D024)Science and Technology Project of Xi
文摘OBJECTIVE Oleoylethanolamide(OEA) is an endogenous peroxisome proliferatoractivated receptor alpha(PPARα) agonist that acts on the peripheral control of energy metabolism.Previous studies have shown that OEA exerts neuroprotection after cerebral ischemia.However,whether OEA affects the outcomes of diabetes-induced encephalopathy(DE) requires further study.METHODS The chronic effects of OEA on DE were evaluated in C57BL/6 and PPARαknockout mice,individually.The cognitive function was assessed with Morris water maze.The expression of receptor for advanced glycation end products(RAGE) and phosphorylation of Tau in mice hippocampus were determined using Western blotting.The influence of OEA in neuron loss and neuroplasticity were assessed with immunofluorescent staining and Western blotting.RESULTS OEA markedly ameliorated performance in the Morris water maze,which was correlated with its capabilities of suppressing glycometabolism and phosphorylation of Tau in the hippocampus.OEA offered protection from diabetes-induced impairments in hippocampal neuroplasticity.Furthermore,the changes in Morris water maze performance and neuron loss could not be observed in PPARα knockout mouse models with OEA administration.CONCLUSION The ability of OEA to control PPARα signaling can serve as a novel neuroprotective approach for the treatment of diabetes-induced encephalopathy.
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.
