title: Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.
abstract: Prenatal Restraint Stress (PRS) in rats is a validated model of early stress resulting in permanent behavioral and neurobiological outcomes. Although sexual dimorphism in the effects of PRS has been hypothesized for more than 30 years, few studies in this long period have directly addressed the issue. Our group has uncovered a pronounced gender difference in the effects of PRS (stress delivered to the mothers 3 times per day during the last 10 days of pregnancy) on anxiety, spatial learning, and a series of neurobiological parameters classically associated with hippocampus-dependent behaviors. Adult male rats subjected to PRS ("PRS rats") showed increased anxiety-like behavior in the elevated plus maze (EPM), a reduction in the survival of newborn cells in the dentate gyrus, a reduction in the activity of mGlu1/5 metabotropic glutamate receptors in the ventral hippocampus, and an increase in the levels of brain-derived neurotrophic factor (BDNF) and pro-BDNF in the hippocampus. In contrast, female PRS rats displayed reduced anxiety in the EPM, improved learning in the Morris water maze, an increase in the activity of mGlu1/5 receptors in the ventral and dorsal hippocampus, and no changes in hippocampal neurogenesis or BDNF levels. The direction of the changes in neurogenesis, BDNF levels and mGlu receptor function in PRS animals was not consistent with the behavioral changes, suggesting that PRS perturbs the interdependency of these particular parameters and their relation to hippocampus-dependent behavior. Our data suggest that the epigenetic changes in hippocampal neuroplasticity induced by early environmental challenges are critically sex-dependent and that the behavioral outcome may diverge in males and females.
authors.affiliation: Perinatal Stress Lab., University Lille 1, Villeneuve d'Ascq, France.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Zuena
authors.forename: Jerome
authors.initials: J
authors.lastname: Mairesse
authors.forename: Paola
authors.initials: P
authors.lastname: Casolini
authors.forename: Carlo
authors.initials: C
authors.lastname: Cinque
authors.forename: Giovanni Sebastiano
authors.initials: GS
authors.lastname: Alemà
authors.forename: Sara
authors.initials: S
authors.lastname: Morley-Fletcher
authors.forename: Valentina
authors.initials: V
authors.lastname: Chiodi
authors.forename: Luigi Giusto
authors.initials: LG
authors.lastname: Spagnoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Gradini
authors.forename: Assia
authors.initials: A
authors.lastname: Catalani
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Stefania
authors.initials: S
authors.lastname: Maccari
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006868:Hydrolysis; D007103:Immobilization; D007858:Learning; D008297:Male; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012737:Sex Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018129:Phosphatidylinositol Phosphates; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1