Prenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in rats

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dc.contributor.authorPalacios-García, Ismael
dc.contributor.authorLara-Vásquez, Ariel
dc.contributor.authorMontiel, Juan F.
dc.contributor.authorDíaz-Véliz, Gabriela F.
dc.contributor.authorSepúlveda, Hugo
dc.contributor.authorUtreras, Elías
dc.contributor.authorMontecino, Martín
dc.contributor.authorGonzález-Billault, Christian
dc.contributor.authorAboitiz, Francisco
dc.date.accessioned2023-07-13T15:44:43Z
dc.date.available2023-07-13T15:44:43Z
dc.date.issued2015-02
dc.descriptionIndexación: Scopuses
dc.description.abstractPrenatal stress causes predisposition to cognitive and emotional disturbances and is a risk factor towards the development of neuropsychiatric conditions like depression, bipolar disorders and schizophrenia. The extracellular protein Reelin, expressed by Cajal-Retzius cells during cortical development, plays critical roles on cortical lamination and synaptic maturation, and its deregulation has been associated with maladaptive conditions. In the present study, we address the effect of prenatal restraint stress (PNS) upon Reelin expression and signaling in pregnant rats during the last 10 days of pregnancy. Animals from one group, including control and PNS exposed fetuses, were sacrificed and analyzed using immunohistochemical, biochemical, cell biology and molecular biology approaches. We scored changes in the expression of Reelin, its signaling pathway and in the methylation of its promoter. A second group included control and PNS exposed animals maintained until young adulthood for behavioral studies. Using the optical dissector, we show decreased numbers of Reelin-positive neurons in cortical layer I of PNS exposed animals. In addition, neurons from PNS exposed animals display decreased Reelin expression that is paralleled by changes in components of the Reelin-signaling cascade, both in vivo and in vitro. Furthermore, PNS induced changes in the DNA methylation levels of the Reelin promoter in culture and in histological samples. PNS adult rats display excessive spontaneous locomotor activity, high anxiety levels and problems of learning and memory consolidation. No significant visuo-spatial memory impairment was detected on the Morris water maze. These results highlight the effects of prenatal stress on the Cajal-Retzius neuronal population, and the persistence of behavioral consequences using this treatment in adults, thereby supporting a relevant role of PNS in the genesis of neuropsychiatric diseases. We also propose an in vitro model that can yield new insights on the molecular mechanisms behind the effects of prenatal stress. © 2015 Palacios-García et al.es
dc.description.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117680
dc.identifier.citationPLoS ONE Volume 10, Issue 213 February 2015 Article number e0117680es
dc.identifier.doi10.1371/journal.pone.0117680
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/51631
dc.language.isoenes
dc.publisherPublic Library of Sciencees
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.titlePrenatal stress down-regulates Reelin expression by methylation of its promoter and induces adult behavioral impairments in ratses
dc.typeArtículoes
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