Dataset Information

Hippocampal PPAR? Overexpression or Activation Represses Stress-Induced Depressive Behaviors and Enhances Neurogenesis.

ABSTRACT:

Background

Emerging data have demonstrated that peroxisome proliferator-activated receptor ? (PPAR?) activation confers a potentially neuroprotective role in some neurodegenerative diseases. However, whether PPAR? is involved in depression is unknown.

Methods

In this study, PPAR? 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 PPAR? overexpression by microinfusion of the lentiviral vector, containing the coding sequence of mouse PPAR? (LV-PPAR?), into the bilateral dentate gyri of the hippocampus or PPAR? activation by repeated systemic administration of PPAR? 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 PPAR? expression in the hippocampi of mice, and this change was reversed by treatment with the antidepressant fluoxetine. PPAR? overexpression and PPAR? 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 PPAR? enhanced proliferation or differentiation of neural stem cells in the hippocampi of mice.

Conclusions

These results suggest that hippocampal PPAR? upregulation represses stress-induced depressive behaviors, accompanied by enhancement of neurogenesis.

SUBMITTER: Ji MJ

PROVIDER: S-EPMC4772271 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Hippocampal PPARδ Overexpression or Activation Represses Stress-Induced Depressive Behaviors and Enhances Neurogenesis.

Ji Miao-Jin MJ Yu Xu-Ben XB Mei Zhen-Lin ZL An Yun-Qi YQ Tang Su-Su SS Hu Mei M Long Yan Y Miao Ming-Xing MX Hu Qing-Hua QH Sun Hong-Bin HB Kong Ling-Yi LY Hong Hao H

The international journal of neuropsychopharmacology 20150910 1

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 26362775

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