ArticleBiological psychiatry2013
Social isolation exacerbates schizophrenia-like phenotypes via oxidative stress in cortical interneurons.
Article in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 129 citations in OpenAlex.
- Parvalbumin interneurons under stress: converging mechanisms of vulnerability.The international journal of neuropsychopharmacology · 2026Review
- Impact of early social isolation on social circuits and behavior: relevance to schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Schizophrenia Pathophysiology: Neurotransmitter Dysfunctions and Biomarker Frontiers.Current topics in medicinal chemistry · 2026Review
- Every-Other-Day Feeding Prevents the Loss of Parvalbumin-Expressing Neurons in the Cerebral Cortex of Female 5xFAD Mice.Molecular neurobiology · 2025Article
- Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.Nature communications · 2025Article
- Application of edaravone-loaded nanogel in alleviating behavioral deficits and oxidative stress in schizophrenia rat model.Scientific reports · 2025Article
- Early postnatal NMDA receptor ablation in cortical interneurons impairs affective state discrimination and social functioning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Social functioning and frontal alpha asymmetry in schizophrenia.Journal of psychiatric research · 2025Article
- Epigallocatechin-3-gallate conjugated with selenium nanoparticles prevents neurological complications in rats exhibiting schizophrenia-like behaviors.Frontiers in pharmacology · 2025Article
- Neural cell-types and circuits linking thermoregulation and social behavior.Neuroscience and biobehavioral reviews · 2024Review
- Differential regulation of innate immune system in frontal cortex and hippocampus in a "double-hit" neurodevelopmental model in rats.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Btbd11 supports cell-type-specific synaptic function.Cell reports · 2023Article
- Sex- and exposure age-dependent effects of adolescent stress on ventral tegmental area dopamine system and its afferent regulators.Molecular psychiatry · 2023Article
- Myelinating Co-Culture as a Model to Study Anti-NMDAR Neurotoxicity.International journal of molecular sciences · 2022Article
- Adaptive changes to oxidative stress in schizophrenia.Molecular psychiatry · 2022Article
- Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia; Response to "Adaptive changes to oxidative stress in schizophrenia by Lena Palaniyappan".Molecular psychiatry · 2022Article
- Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia.Molecular psychiatry · 2022Review
- Abnormal oligodendrocyte function in schizophrenia explains the long latent interval in some patients.Translational psychiatry · 2022Review
- Clinical translational neuroimaging of the antioxidant effect of N-acetylcysteine on neural microstructure.Magnetic resonance in medicine · 2022Article
- Dysregulation of prefrontal parvalbumin interneurons leads to adult aggression induced by social isolation stress during adolescence.Frontiers in molecular neuroscience · 2022Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOur previous studies indicated that N-methyl-D-aspartate receptor (NMDAR) deletion from a subset of corticolimbic interneurons in the mouse brain during early postnatal development is sufficient to trigger several behavioral and pathophysiological features resembling the symptoms of human schizophrenia. Interestingly, many of these behavioral phenotypes are exacerbated by social isolation stress. However, the mechanisms underlying the exacerbating effects of social isolation are unclear.
methodsWith γ-aminobutyric acid-ergic interneuron-specific NMDAR hypofunction mouse model (Ppp1r2-Cre/fGluN1 knockout [KO] mice), we investigated whether oxidative stress is implicated in the social isolation-induced exacerbation of schizophrenia-like phenotypes and further explored the underlying mechanism of elevated oxidative stress in KO mice.
resultsThe reactive oxygen species (ROS) level in the cortex of group-housed KO mice was normal at 8 weeks although increased at 16 weeks old. Postweaning social isolation (PWSI) augmented the ROS levels in KO mice at both ages, which was accompanied by the onset of behavioral phenotype. Chronic treatment with apocynin, an ROS scavenger, abolished markers of oxidative stress and partially alleviated schizophrenia-like behavioral phenotypes in KO mice. Markers of oxidative stress after PWSI were especially prominent in cortical parvalbumin (PV)-positive interneurons. The vulnerability of PV interneurons to oxidative stress was associated with downregulation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a master regulator of mitochondrial energy metabolism and antioxidation.
conclusionsThese results suggest that a PWSI-mediated impairment in antioxidant defense mechanisms, presumably mediated by PGC-1α downregulation in the NMDAR-deleted PV-positive interneurons, results in oxidative stress, which, in turn, might contribute to exacerbation of schizophrenia-like behavioral phenotypes.
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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.