ArticleMolecular metabolism2015
Peroxisome proliferator-activated receptor alpha plays a crucial role in behavioral repetition and cognitive flexibility in mice.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- Astrocyte fatty acid metabolism as a driver of risk for major depressive disorder.Nature communications · 2026Article
- Predifferentiation Neurotoxicity of GenX Exposure on hiPSC-Derived Cortical Neurons.Environmental science & technology · 2026Article
- Low-dose combination of ultramicronized palmitoylethanolamide and docosahexaenoic acid on neurosteroid and neuroinflammatory dysregulation in autism spectrum disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Article
- Deciphering the Role of Peroxisome Proliferator-activated Receptor α and Phosphodiesterase Type 5 Targets in Alzheimer's Disease.CNS & neurological disorders drug targets · 2024Review
- Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders.Nutrients · 2023Review
- Nurture outpaces nature: fostering with an attentive mother alters social dominance in a mouse model of stress sensitivity.Molecular psychiatry · 2023Article
- PPARα Signaling: A Candidate Target in Psychiatric Disorder Management.Biomolecules · 2022Review
- Regulation of PPARα by APP in Alzheimer disease affects the pharmacological modulation of synaptic activity.JCI insight · 2021Article
- Persistent proteomic changes in glutamatergic and GABAergic signaling in the amygdala of adolescent rats exposed to chlorpyrifos as juveniles.Neurotoxicology · 2021Article
- Review
- Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant.Frontiers in pharmacology · 2021Article
- Targeting PPARα in the rat valproic acid model of autism: focus on social motivational impairment and sex-related differences.Molecular autism · 2020Article
- Alzheimer's Disease, a Lipid Story: Involvement of Peroxisome Proliferator-Activated Receptor α.Cells · 2020Review
- The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer's Disease and Other Neurodegenerative Disorders.Neurochemical research · 2020Review
- Inhibition of fatty acid amide hydrolase by chlorpyrifos in juvenile rats results in altered exploratory and social behavior as adolescents.Neurotoxicology · 2020Article
- Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?Molecules (Basel, Switzerland) · 2020Review
- Treatment With 2-Pentadecyl-2-Oxazoline Restores Mild Traumatic Brain Injury-Induced Sensorial and Neuropsychiatric Dysfunctions.Frontiers in pharmacology · 2020Article
- Nuclear Peroxisome Proliferator-Activated Receptors (PPARs) as Therapeutic Targets of Resveratrol for Autism Spectrum Disorder.International journal of molecular sciences · 2019Review
- Sex-regulated gene dosage effect of PPARα on synaptic plasticity.Life science alliance · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
objectivesNuclear peroxisome proliferator activated receptor-α (PPAR-α) plays a fundamental role in the regulation of lipid homeostasis and is the target of medications used to treat dyslipidemia. However, little is known about the role of PPAR-α in mouse behavior.
methodsTo investigate the function of Ppar-α in cognitive functions, a behavioral phenotype analysis of mice with a targeted genetic disruption of Ppar-α was performed in combination with neuroanatomical, biochemical and pharmacological manipulations. The therapeutic exploitability of PPAR-α was probed in mice using a pharmacological model of psychosis and a genetic model (BTBR T + tf/J) exhibiting a high rate of repetitive behavior.
resultsAn unexpected role for brain Ppar-α in the regulation of cognitive behavior in mice was revealed. Specifically, we observed that Ppar-α genetic perturbation promotes rewiring of cortical and hippocampal regions and a behavioral phenotype of cognitive inflexibility, perseveration and blunted responses to psychomimetic drugs. Furthermore, we demonstrate that the antipsychotic and autism spectrum disorder (ASD) medication risperidone ameliorates the behavioral profile of Ppar-α deficient mice. Importantly, we reveal that pharmacological PPAR-α agonist treatment in mice improves behavior in a pharmacological model of ketamine-induced behavioral dysinhibition and repetitive behavior in BTBR T + tf/J mice.
conclusionOur data indicate that Ppar-α is required for normal cognitive function and that pharmacological stimulation of PPAR-α improves cognitive function in pharmacological and genetic models of impaired cognitive function in mice. These results thereby reveal an unforeseen therapeutic application for a class of drugs currently in human use.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.