ArticleThe international journal of neuropsychopharmacology2019
Hippocampal Genetic Knockdown of PPARδ Causes Depression-Like Behaviors and Neurogenesis Suppression.
Article in The international journal of neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Effect of Multivoice Chorus on Interpersonal Communication Disorder.Occupational therapy international · 2022Trial
- DNMT1 function in cortical PV interneurons modulates cortical network activity, mood disorder‑related behavior, and perineuronal nets.Communications biology · 2026Article
- Pathophysiological roles of neural stem cells in neuropsychiatric diseases: from plasticity to pharmacological targeting.Acta pharmacologica Sinica · 2026Review
- Genome-wide association study identifies novel variants in olfactory, vitamin A, vitamin B, and cadherin pathways associated with learning and memory.Scientific reports · 2025Article
- Impaired neural activity and functional connectivity in the hippocampus of adolescents with non-suicidal self-injury addiction.BMC psychiatry · 2025Article
- Administration of chiglitazar reverses chronic stress-induced depressive-like symptoms in mice via activation of hippocampal PPARα and BDNF.Frontiers in pharmacology · 2025Article
- Stress-related cellular pathophysiology as a crosstalk risk factor for neurocognitive and psychiatric disorders.BMC neuroscience · 2023Review
- Novel Pharmacological Approaches to the Treatment of Depression.Life (Basel, Switzerland) · 2022Review
- Nuclear receptors modulate inflammasomes in the pathophysiology and treatment of major depressive disorder.World journal of psychiatry · 2021Review
- Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature.Brain sciences · 2021Review
- PPARD May Play a Protective Role for Major Depressive Disorder.PPAR research · 2021Article
- Variants and expression changes in PPAR-encoding genes display no significant association with schizophrenia.Bioscience reports · 2020Observational
- Free Fatty Acids and Their Inflammatory Derivatives Affect BDNF in Stroke Patients.Mediators of inflammation · 2020Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough 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.
methodsStereotaxic 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.
resultsHippocampal 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).
conclusionsThese 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.
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