Molecular mechanisms underlying glutamatergic dysfunction in schizophrenia: Therapeutic implications
Author
dc.contributor.author
Gaspar, Pablo A.
Author
dc.contributor.author
Bustamante, M. Leonor
Author
dc.contributor.author
Silva, Hernán
Author
dc.contributor.author
Aboitiz, Francisco
Admission date
dc.date.accessioned
2018-12-20T14:12:23Z
Available date
dc.date.available
2018-12-20T14:12:23Z
Publication date
dc.date.issued
2009
Cita de ítem
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Journal of Neurochemistry, Volumen 111, Issue 4, 2018, Pages 891-900
Identifier
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00223042
Identifier
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14714159
Identifier
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10.1111/j.1471-4159.2009.06325.x
Identifier
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https://repositorio.uchile.cl/handle/2250/154753
Abstract
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Early models for the etiology of schizophrenia focused on dopamine neurotransmission because of the powerful anti-psychotic action of dopamine antagonists. Nevertheless, recent evidence increasingly supports a primarily glutamatergic dysfunction in this condition, where dopaminergic disbalance is a secondary effect. A current model for the pathophysiology of schizophrenia involves a dysfunctional mechanism by which the NMDA receptor (NMDAR) hypofunction leads to a dysregulation of GABA fast- spiking interneurons, consequently disinhibiting pyramidal glutamatergic output and disturbing the signal-to-noise ratio. This mechanism might explain better than other models some cognitive deficits observed in this disease, as well as the dopaminergic alterations and therapeutic effect of anti-psychotics. Although the modulation of glutamate activity has, in principle, great therapeutic potential, a side effect of NMDAR overactivation is neurotoxicity, which accelerates neuropathological alterati