Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations

Behavioural Brain Research
Aline Santos MonteDanielle Silveira Macêdo

Abstract

Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5-7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatu...Continue Reading

Citations

Sep 27, 2019·Journal of Psychopharmacology·Aline Santos MonteDanielle S Macedo
Feb 29, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jonathan A HollanderChristine Ladd-Acosta
Aug 11, 2020·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Dong Mei WangXiang Yang Zhang
Jan 4, 2019·Journal of Molecular Neuroscience : MN·Joanna A RuszkiewiczMichael Aschner
Oct 27, 2020·Frontiers in Psychiatry·Veronika LangovaJiri Horacek
Jan 31, 2021·Developmental Cognitive Neuroscience·Kelsea R GildawieHeather C Brenhouse
Mar 14, 2020·Pharmacology & Therapeutics·Andrea Carlo RossettiRaffaella Molteni
Mar 16, 2019·Brain, Behavior, and Immunity·Marion RincelMuriel Darnaudéry
Apr 28, 2021·Progress in Neurobiology·Navneet A Vasistha, Konstantin Khodosevich
Apr 28, 2021·Translational Psychiatry·Laiana A QuagliatoAntonio E Nardi
May 14, 2021·Progress in Neuro-psychopharmacology & Biological Psychiatry·Germana Silva VasconcelosDanielle S Macedo

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