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Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.

Zuena AR, Mairesse J, Casolini P, Cinque C, Alemà GS, Morley-Fletcher S, Chiodi V, Spagnoli LG, Gradini R, Catalani A, Nicoletti F, Maccari S - PLoS ONE (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Perinatal Stress Lab., University Lille 1, Villeneuve d'Ascq, France.

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.

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PRS enhances hippocampal BDNF levels in male rats.(A) Immunoblot analysis showed a 14 kDa band which corresponds to the mature form of BDNF, and a higher molecular weight band (about 35 kDa), which may correspond to its precursor, pro-BDNF. (B) PRS increased the steady-state levels of both BDNF and pro-BDNF in male rats (* p<0.05, ANOVA: F (1,12) = 29.68, F (1,12) = 27.09, respectively,), but had no effect in female rats. Male and female hippocampi were processed separately. Results are expressed as the ratio of the optical density (OD) of the pro-BDNF or BDNF band and the β-actin band. Values are expressed as means±S.E.M. (n = 7 rats per group).
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pone-0002170-g004: PRS enhances hippocampal BDNF levels in male rats.(A) Immunoblot analysis showed a 14 kDa band which corresponds to the mature form of BDNF, and a higher molecular weight band (about 35 kDa), which may correspond to its precursor, pro-BDNF. (B) PRS increased the steady-state levels of both BDNF and pro-BDNF in male rats (* p<0.05, ANOVA: F (1,12) = 29.68, F (1,12) = 27.09, respectively,), but had no effect in female rats. Male and female hippocampi were processed separately. Results are expressed as the ratio of the optical density (OD) of the pro-BDNF or BDNF band and the β-actin band. Values are expressed as means±S.E.M. (n = 7 rats per group).

Mentions: We examined the expression of BDNF in the hippocampus by immunoblotting. The blot revealed a 14 kDa band which corresponds to the mature form of BDNF, and a higher molecular weight band (about 35 kDa), which may correspond to its precursor, pro-BDNF (Fig. 4A). PRS increased the steady-state levels of both BDNF and pro-BDNF in male rats, but had no effect in female rats (Fig. 4A,B). The increase in both BDNF and pro-BDNF suggests enhanced BDNF production/transcription/expression in the hippocampus of male rats exposed to PRS.


Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats.

Zuena AR, Mairesse J, Casolini P, Cinque C, Alemà GS, Morley-Fletcher S, Chiodi V, Spagnoli LG, Gradini R, Catalani A, Nicoletti F, Maccari S - PLoS ONE (2008)

PRS enhances hippocampal BDNF levels in male rats.(A) Immunoblot analysis showed a 14 kDa band which corresponds to the mature form of BDNF, and a higher molecular weight band (about 35 kDa), which may correspond to its precursor, pro-BDNF. (B) PRS increased the steady-state levels of both BDNF and pro-BDNF in male rats (* p<0.05, ANOVA: F (1,12) = 29.68, F (1,12) = 27.09, respectively,), but had no effect in female rats. Male and female hippocampi were processed separately. Results are expressed as the ratio of the optical density (OD) of the pro-BDNF or BDNF band and the β-actin band. Values are expressed as means±S.E.M. (n = 7 rats per group).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2366064&req=5

pone-0002170-g004: PRS enhances hippocampal BDNF levels in male rats.(A) Immunoblot analysis showed a 14 kDa band which corresponds to the mature form of BDNF, and a higher molecular weight band (about 35 kDa), which may correspond to its precursor, pro-BDNF. (B) PRS increased the steady-state levels of both BDNF and pro-BDNF in male rats (* p<0.05, ANOVA: F (1,12) = 29.68, F (1,12) = 27.09, respectively,), but had no effect in female rats. Male and female hippocampi were processed separately. Results are expressed as the ratio of the optical density (OD) of the pro-BDNF or BDNF band and the β-actin band. Values are expressed as means±S.E.M. (n = 7 rats per group).
Mentions: We examined the expression of BDNF in the hippocampus by immunoblotting. The blot revealed a 14 kDa band which corresponds to the mature form of BDNF, and a higher molecular weight band (about 35 kDa), which may correspond to its precursor, pro-BDNF (Fig. 4A). PRS increased the steady-state levels of both BDNF and pro-BDNF in male rats, but had no effect in female rats (Fig. 4A,B). The increase in both BDNF and pro-BDNF suggests enhanced BDNF production/transcription/expression in the hippocampus of male rats exposed to PRS.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Perinatal Stress Lab., University Lille 1, Villeneuve d'Ascq, France.

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.

Show MeSH