کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2494203 1115550 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex?
چکیده انگلیسی

An imbalance in the redox-state of the brain may be part of the underlying pathophysiology in schizophrenia. Inflammatory mediators, such as IL-6, which can tip the redox balance into a pro-oxidant state, have been consistently found to be altered in schizophrenia patients. However, the relationship of altered redox-state to altered brain functions observed in the disease has been unclear. Recent data from a pharmacological model of schizophrenia suggest that redox and inflammatory imbalances may be directly linked to the pathophysiology of the disease by alterations in fast-spiking interneurons. Repetitive adult exposure to the NMDA-R antagonist ketamine increases the levels of the proinflammatory cytokine interleukin-6 in brain which, through activation of the superoxide-producing enzyme NADPH oxidase (Nox2), leads to the loss of the GABAergic phenotype of PV-interneurons and to decreased inhibitory activity in prefrontal cortex. This effect is not observed after a single exposure to ketamine, suggesting that the first exposure to the NMDA-R antagonist primes the brain such that deleterious effects on PV-interneurons appear upon repetitive exposures. The effects of activation of the IL-6/Nox2 pathway on the PV-interneuronal system are reversible in the adult brain, but permanent in the developing cortex. The slow development of PV-interneurons, although essential for shaping of neuronal circuits during postnatal brain development, increases their vulnerability to deleterious insults that can permanently affect their maturational process. Thus, in individuals with genetic predisposition, the persistent activation of the IL-6/Nox2 pathway may be an environmental factor that tips the redox balance leading to schizophrenia symptoms in late adolescence and early adulthood.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 57, Issue 3, September 2009, Pages 193–200
نویسندگان
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