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

Autor: Joseph T. Coyle, Anthony-Samuel LaMantia, Lothar Lindemann, Hirofumi Morishita, Michael Didriksen, Kim Q. Do, Michel Cuenod, Matthew D. Puhl, Jan-Harry Cabungcal, Urs Meyer, Takao K. Hensch, Patricio O'Donnell, Pascal Steullet, Anthony A. Grace, Thomas M. Maynard, K Gill
Přispěvatelé: University of Zurich, Do, K Q
Rok vydání: 2016
Předmět:
0301 basic medicine
Interneuron
Autism Spectrum Disorder
2804 Cellular and Molecular Neuroscience
medicine.disease_cause
Gyrus Cinguli
Animals
Autism Spectrum Disorder/genetics
Autism Spectrum Disorder/metabolism
Disease Models
Animal
Gyrus Cinguli/metabolism
Humans
Interneurons/metabolism
Interneurons/physiology
Mice
Oxidation-Reduction
Oxidative Stress/genetics
Oxidative Stress/physiology
Parvalbumins/metabolism
Schizophrenia/genetics
Schizophrenia/metabolism
2738 Psychiatry and Mental Health
03 medical and health sciences
Cellular and Molecular Neuroscience
Glutamatergic
0302 clinical medicine
Interneurons
1312 Molecular Biology
medicine
Molecular Biology
biology
Mechanism (biology)
Perineuronal net
10079 Institute of Veterinary Pharmacology and Toxicology
medicine.disease
Psychiatry and Mental health
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Parvalbumins
Schizophrenia
Perspective
biology.protein
570 Life sciences
Autism
Psychology
Neuroscience
030217 neurology & neurosurgery
Parvalbumin
Oxidative stress
Zdroj: Molecular Psychiatry
Molecular psychiatry, vol. 22, no. 7, pp. 936-943
ISSN: 1476-5578
Popis: 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.
Databáze: OpenAIRE
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