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dc.contributor.author
Nakazawa, Kazu
dc.contributor.author
Zsiros, Veronika
dc.contributor.author
Jiang, Zhihong
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Nakao, Kazuhito
dc.contributor.author
Kolata, Stefan
dc.contributor.author
Zhang, Shuqin
dc.contributor.author
Belforte, Juan Emilio
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dc.date.available
2023-03-29T14:35:08Z
dc.date.issued
2012-03
dc.identifier.citation
Nakazawa, Kazu; Zsiros, Veronika; Jiang, Zhihong; Nakao, Kazuhito; Kolata, Stefan; et al.; GABAergic interneuron origin of schizophrenia pathophysiology; Pergamon-Elsevier Science Ltd; Neuropharmacology; 62; 3; 3-2012; 1574-1583
dc.identifier.issn
0028-3908
dc.identifier.uri
http://hdl.handle.net/11336/192003
dc.description.abstract
Hypofunction of N-methyl-d-aspartic acid-type glutamate receptors (NMDAR) induced by the systemic administration of NMDAR antagonists is well known to cause schizophrenia-like symptoms in otherwise healthy subjects. However, the brain areas or cell-types responsible for the emergence of these symptoms following NMDAR hypofunction remain largely unknown. One possibility, the so-called "GABAergic origin hypothesis," is that NMDAR hypofunction at GABAergic interneurons, in particular, is sufficient for schizophrenia-like effects. In one attempt to address this issue, transgenic mice were generated in which NMDARs were selectively deleted from cortical and hippocampal GABAergic interneurons, a majority of which were parvalbumin (PV)-positive. This manipulation triggered a constellation of phenotypes-from molecular and physiological to behavioral-resembling characteristics of human schizophrenia. Based on these results, and in conjunction with previous literature, we argue that during development, NMDAR hypofunction at cortical, PV-positive, fast-spiking interneurons produces schizophrenia-like effects. This review summarizes the data demonstrating that in schizophrenia, GABAergic (particularly PV-positive) interneurons are disrupted. PV-positive interneurons, many of which display a fast-spiking firing pattern, are critical not only for tight temporal control of cortical inhibition but also for the generation of synchronous membrane-potential gamma-band oscillations. We therefore suggest that in schizophrenia the specific ability of fast-spiking interneurons to control and synchronize disparate cortical circuits is disrupted and that this disruption may underlie many of the schizophrenia symptoms. We further argue that the high vulnerability of corticolimbic fast-spiking interneurons to genetic predispositions and to early environmental insults-including excitotoxicity and oxidative stress-might help to explain their significant contribution to the development of schizophrenia.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
FAST-SPIKING INTERNEURON
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NMDA RECEPTOR HYPOFUNCTION
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OXIDATIVE STRESS
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PARVALBUMIN
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SCHIZOPHRENIA
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TRANSGENIC MICE
dc.subject.classification
Neurociencias
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
GABAergic interneuron origin of schizophrenia pathophysiology
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-03-23T12:25:35Z
dc.journal.volume
62
dc.journal.number
3
dc.journal.pagination
1574-1583
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Nakazawa, Kazu. National Institute of Mental Health; Estados Unidos
dc.description.fil
Fil: Zsiros, Veronika. National Institute of Mental Health; Estados Unidos
dc.description.fil
Fil: Jiang, Zhihong. National Institute of Mental Health; Estados Unidos
dc.description.fil
Fil: Nakao, Kazuhito. National Institute of Mental Health; Estados Unidos
dc.description.fil
Fil: Kolata, Stefan. National Institute of Mental Health; Estados Unidos
dc.description.fil
Fil: Zhang, Shuqin. National Institute of Mental Health; Estados Unidos
dc.description.fil
Fil: Belforte, Juan Emilio. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Neuropharmacology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0028390811000256
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.neuropharm.2011.01.022
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