Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
Biol. Res
; 49: 1-10, 2016. ilus, graf
Article
em En
| LILACS
| ID: biblio-950843
Biblioteca responsável:
CL1.1
ABSTRACT
Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene.
Palavras-chave
Texto completo:
1
Bases de dados:
LILACS
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
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Esquizofrenia
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Estresse Fisiológico
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Encéfalo
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Serina Endopeptidases
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Moléculas de Adesão Celular Neuronais
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Proteínas da Matriz Extracelular
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Epigênese Genética
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Proteínas do Tecido Nervoso
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Biol. Res
Assunto da revista:
BIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Chile