期刊
CURRENT OPINION IN NEUROBIOLOGY
卷 19, 期 2, 页码 220-230出版社
CURRENT BIOLOGY LTD
DOI: 10.1016/j.conb.2009.05.001
关键词
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资金
- Swiss National Foundation [310000-116689]
- 'Loterie Romande'
- NARSAD
- Alamaya Foundation
In schizophrenia, a developmental redox dysregulation constitutes one 'hub' on which converge genetic impairments of glutathione synthesis and environmental vulnerability factors generating oxidative stress. Their timing at critical periods of neurodevelopment could play a decisive role in inducing impairment of neural connectivity and synchronization as observed in schizophrenia. In experimental models, such redox dysregulation induces anomalies strikingly similar to those observed in patients. This is mediated by hypoactive NMDA receptors, impairment of fast-spiking parvalbumin GABA interneurons and deficit in myelination. A treatment restoring the redox balance without side effects yields improvements of negative symptoms in chronic patients. Novel interventions based on these mechanisms if applied in early phases of the disease hold great therapeutic promise.
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