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Mol Psychiatry. 2017 Jul;22(7):936-943. doi: 10.1038/mp.2017.47. Epub 2017 Mar 21.

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

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Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly-Lausanne, Switzerland.
Laboratory for Psychiatric and Molecular Neuroscience, Harvard Medical School, McLean Hospital, Belmont, MA, USA.
Synaptic transmission H. Lundbeck A/S, Valby, Denmark.
Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
Center for Brain Science, Department of Molecular Cellular Biology, Harvard University, Cambridge, MA USA.
FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
George Washington Institute for Neuroscience, The George Washington University, Washington, DC, USA.
F. Hoffmann-La Roche, Roche Pharmaceutical and Early Development, Neuroscience, Opthalmology &Rare Disease (NORD) DTA, Discovery Neuroscience, Roche Innovation Center Basel, Basel, Switzerland.
Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.
Department of Psychiatry, Neuroscience, and Ophthalmology, Friedman Brain Institute, Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, NY, USA.
Neuroscience and Pain Research Unit, BioTherapeutics Research and Development, Pfizer, Cambridge, MA, USA.


Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress.

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