Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior

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 wit...

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Autores principales:	Negrón-Oyarzo,Ignacio, Lara-Vásquez,Ariel, Palacios-García,Ismael, Fuentealba,Pablo, Aboitiz,Francisco
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2016
Materias:	Schizophrenia Prefrontal cortex Prenatal stress Functional connectivity DNA methylation Reelin
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602016000100016
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spelling	oai:scielo:S0716-976020160001000162016-12-01Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behaviorNegrón-Oyarzo,IgnacioLara-Vásquez,ArielPalacios-García,IsmaelFuentealba,PabloAboitiz,Francisco Schizophrenia Prefrontal cortex Prenatal stress Functional connectivity DNA methylation Reelin 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.49 20162016-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602016000100016en10.1186/s40659-016-0076-5
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Schizophrenia Prefrontal cortex Prenatal stress Functional connectivity DNA methylation Reelin
spellingShingle	Schizophrenia Prefrontal cortex Prenatal stress Functional connectivity DNA methylation Reelin Negrón-Oyarzo,Ignacio Lara-Vásquez,Ariel Palacios-García,Ismael Fuentealba,Pablo Aboitiz,Francisco Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
description	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.
author	Negrón-Oyarzo,Ignacio Lara-Vásquez,Ariel Palacios-García,Ismael Fuentealba,Pablo Aboitiz,Francisco
author_facet	Negrón-Oyarzo,Ignacio Lara-Vásquez,Ariel Palacios-García,Ismael Fuentealba,Pablo Aboitiz,Francisco
author_sort	Negrón-Oyarzo,Ignacio
title	Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
title_short	Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
title_full	Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
title_fullStr	Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
title_full_unstemmed	Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
title_sort	schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
publisher	Sociedad de Biología de Chile
publishDate	2016
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602016000100016
work_keys_str_mv	AT negronoyarzoignacio schizophreniaandreelinamodelbasedonprenatalstresstostudyepigeneticsbraindevelopmentandbehavior AT laravasquezariel schizophreniaandreelinamodelbasedonprenatalstresstostudyepigeneticsbraindevelopmentandbehavior AT palaciosgarciaismael schizophreniaandreelinamodelbasedonprenatalstresstostudyepigeneticsbraindevelopmentandbehavior AT fuentealbapablo schizophreniaandreelinamodelbasedonprenatalstresstostudyepigeneticsbraindevelopmentandbehavior AT aboitizfrancisco schizophreniaandreelinamodelbasedonprenatalstresstostudyepigeneticsbraindevelopmentandbehavior
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Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior

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