ArticleBritish journal of pharmacology2018
Hippocampal PPARα is a novel therapeutic target for depression and mediates the antidepressant actions of fluoxetine in mice.
Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 71 citations in OpenAlex.
- Article
- Article
- Metabolic Modulators in Depression: Emerging Molecular Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Pemafibrate treatment produces antidepressant-like effects in CUMS and CRS models through activation of hippocampal PPARα and BDNF signaling.The international journal of neuropsychopharmacology · 2025Article
- The Alpha-7 Nicotinic Receptor Positive Allosteric Modulator PNU120596 Attenuates Lipopolysaccharide-Induced Depressive-Like Behaviors and Cognitive Impairment by Regulating the PPAR-α Signaling Pathway in Mice.CNS & neurological disorders drug targets · 2025Article
- Administration of chiglitazar reverses chronic stress-induced depressive-like symptoms in mice via activation of hippocampal PPARα and BDNF.Frontiers in pharmacology · 2025Article
- Integrative omics analysis reveals epigenomic and transcriptomic signatures underlying brain structural deficits in major depressive disorder.Translational psychiatry · 2024Article
- Activation of mTORC1 Signaling Cascade in Hippocampus and Medial Prefrontal Cortex Is Required for Antidepressant Actions of Vortioxetine in Mice.The international journal of neuropsychopharmacology · 2023Article
- A tau fragment links depressive-like behaviors and cognitive declines in Alzheimer's disease mouse models through attenuating mitochondrial function.Frontiers in aging neuroscience · 2023Article
- The Strategy of Targeting Peroxisome Proliferator-Activated Receptor (PPAR) in the Treatment of Neuropsychiatric Disorders.Advances in experimental medicine and biology · 2023Article
- PPARα Signaling: A Candidate Target in Psychiatric Disorder Management.Biomolecules · 2022Review
- Disruption of 5-hydroxytryptamine 1A receptor and orexin receptor 1 heterodimer formation affects novel G protein-dependent signaling pathways and has antidepressant effects in vivo.Translational psychiatry · 2022Article
- Central Adiponectin Signaling - A Metabolic Regulator in Support of Brain Plasticity.Brain plasticity (Amsterdam, Netherlands) · 2022Review
- Indole-3-Carbinol Selectively Prevents Chronic Stress-Induced Depression-but not Anxiety-Like Behaviors via Suppressing Pro-Inflammatory Cytokine Production and Oxido-Nitrosative Stress in the Brain.Frontiers in pharmacology · 2022Article
- Repurposing Peroxisome Proliferator-Activated Receptor Agonists in Neurological and Psychiatric Disorders.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.Journal of neuroinflammation · 2021Article
- Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant.Frontiers in pharmacology · 2021Article
- LIMK1/2 in the mPFC Plays a Role in Chronic Stress-Induced Depressive-Like Effects in Mice.The international journal of neuropsychopharmacology · 2020Article
- Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?Molecules (Basel, Switzerland) · 2020Review
- The Selective SIK2 Inhibitor ARN-3236 Produces Strong Antidepressant-Like Efficacy in Mice via the Hippocampal CRTC1-CREB-BDNF Pathway.Frontiers in pharmacology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeDeveloping novel pharmacological targets beyond the monoaminergic system is now a popular strategy for treating depression. PPARα is a nuclear receptor protein that functions as a transcription factor,-regulating gene expression. We have previously reported that both WY14643 and fenofibrate, two pharmacological agonists of PPARα, have antidepressant-like effects in mice, implying that PPARα is a potential antidepressant target. EXPERIMENTAL APPROACH: We first used various biotechnological methods to evaluate the effects of chronic stress and fluoxetine on hippocampal PPARα. The viral-mediated genetic approach was then employed to explore whether hippocampal PPARα was an antidepressant target. PPARα inhibitors, PPARα-knockout (KO) mice and PPARα-knockdown (KD) mice were further used to determine the role of PPARα in the antidepressant effects of fluoxetine. KEY
resultsChronic stress significantly decreased mRNA and protein levels of PPARα in the hippocampus, but not other regions, and also fully reduced the recruitment of hippocampal PPARα to the cAMP response element-binding (CREB) promoter. Genetic overexpression of hippocampal PPARα induced significant antidepressant-like actions in mice by promoting CREB-mediated biosynthesis of brain-derived neurotrophic factor. Moreover, fluoxetine notably restored the stress-induced negative effects on hippocampal PPARα. Using PPARα antagonists fully blocked the antidepressant effects of fluoxetine in mice, and similarly, both PPARα-KO and PPARα-KD abolished the effects of fluoxetine. Besides, PPARα-KO and PPARα-KD aggravated depression in mice. CONCLUSIONS AND IMPLICATIONS: Hippocampal PPARα is a potential novel antidepressant target that mediates the antidepressant actions of fluoxetine in mice.
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