title: Hippocampal PPARδ Overexpression or Activation Represses Stress-Induced Depressive Behaviors and Enhances Neurogenesis.
abstract: 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.
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Miao-Jin
authors.initials: MJ
authors.lastname: Ji
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Xu-Ben
authors.initials: XB
authors.lastname: Yu
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Mei
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Yun-Qi
authors.initials: YQ
authors.lastname: An
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Su-Su
authors.initials: SS
authors.lastname: Tang
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Mei
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Yan
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Ming-Xing
authors.initials: MX
authors.lastname: Miao
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Hu
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Sun
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
authors.affiliation: Department of Pharmacology (Ms Ji, Mr Yu, Ms Mei, Ms An, Ms Tang, Ms Hu, Dr Long, Dr Miao, Dr Hu, and Dr Hong), Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases (Ms Ji, Mr Yu, Ms Mei, Dr Hong, and Dr Sun), and State Key Laboratory of Natural Medicines (Ms Ji, Mr Yu, Ms Mei, Dr Kong, and Dr Hong), China Pharmaceutical University, Nanjing. honghao@cpu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003863:Depression / Q000150:complications* / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012844:Sincalide / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications*; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014161:Transduction, Genetic; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D005904:Glial Fibrillary Acidic Protein; D047494:PPAR delta; D010751:Phosphopyruvate Hydratase; D012844:Sincalide; D013844:Thiazoles; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds
keywords: Depression; hippocampal neurogenesis; peroxisome proliferator-activated receptors δ