Limits...
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.

Show MeSH
Hippocampal neurogenesis and gliogenesis in control and PRS rats.Representative confocal laser scanning microscope image showing cells double-labeled for BrdU (red nuclear staining) and the neuronal marker NeuN (green nuclear staining) (A), and cells double-labeled for BrdU and the glial marker GFAP (green cytoplasmic staining) (B). DG: dentate gyrus; GCL: granular cell layer; arrows: double labeled cells. Scale bars-20 µm. (C,D) PRS did not affect the percentage of NeuN+/BrdU+ cells or the percentage of GFAP+/BrdU+ cells within the total population of BrdU+ cells in male and female rats. It is worth noting, however, that both control and PRS female rats showed more efficient gliogenesis, as reflected by a greater percentage of GFAP+/BrdU+ cells than in male rats (# p<0.05 ANOVA sex effect: F (1,16) = 6.48,). (E) PRS reduced the total number of BrdU+/NeuN+ cells in male rats (* p<0.05, ANOVA+Newman-Keul's post-hoc test), with no effect in female rats. (F) PRS had no effect on astroglial differentiation; female rats, independent of group, showed an increase in the total number of newly-formed astroglial cells (# p<0.05, ANOVA sex effect: F (1,16) = 4,53). Bars represent means±SEM (n = 5 rats per group).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2366064&req=5

pone-0002170-g003: Hippocampal neurogenesis and gliogenesis in control and PRS rats.Representative confocal laser scanning microscope image showing cells double-labeled for BrdU (red nuclear staining) and the neuronal marker NeuN (green nuclear staining) (A), and cells double-labeled for BrdU and the glial marker GFAP (green cytoplasmic staining) (B). DG: dentate gyrus; GCL: granular cell layer; arrows: double labeled cells. Scale bars-20 µm. (C,D) PRS did not affect the percentage of NeuN+/BrdU+ cells or the percentage of GFAP+/BrdU+ cells within the total population of BrdU+ cells in male and female rats. It is worth noting, however, that both control and PRS female rats showed more efficient gliogenesis, as reflected by a greater percentage of GFAP+/BrdU+ cells than in male rats (# p<0.05 ANOVA sex effect: F (1,16) = 6.48,). (E) PRS reduced the total number of BrdU+/NeuN+ cells in male rats (* p<0.05, ANOVA+Newman-Keul's post-hoc test), with no effect in female rats. (F) PRS had no effect on astroglial differentiation; female rats, independent of group, showed an increase in the total number of newly-formed astroglial cells (# p<0.05, ANOVA sex effect: F (1,16) = 4,53). Bars represent means±SEM (n = 5 rats per group).

Mentions: Newly-formed neurons and astrocytes were identified by double BrdU/NeuN or BrdU/GFAP immunolabeling (Fig. 3A,B). In male rats, PRS reduced the total number of BrdU+/NeuN+ cells (Fig. 3E), but did not change the percentage of NeuN+ cells within the total population of BrdU+ cells (Fig. 3C). Thus, the reduction in newly-formed neurons did not reflect an effect of PRS on cell differentiation, but was secondary to the overall reduction in BrdU+ cells. PRS did not change the number of NeuN+/BrdU+ cells in female rats (Fig. 3C,E), or the number of GFAP+/BrdU+ cells in either male or female rats (Fig. 3D,F). It is worth noting, however, that both control and PRS female rats showed more efficient gliogenesis, as reflected by a greater number and percentage of GFAP+/BrdU+ cells than in male rats (Fig. 3D,F).


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)

Hippocampal neurogenesis and gliogenesis in control and PRS rats.Representative confocal laser scanning microscope image showing cells double-labeled for BrdU (red nuclear staining) and the neuronal marker NeuN (green nuclear staining) (A), and cells double-labeled for BrdU and the glial marker GFAP (green cytoplasmic staining) (B). DG: dentate gyrus; GCL: granular cell layer; arrows: double labeled cells. Scale bars-20 µm. (C,D) PRS did not affect the percentage of NeuN+/BrdU+ cells or the percentage of GFAP+/BrdU+ cells within the total population of BrdU+ cells in male and female rats. It is worth noting, however, that both control and PRS female rats showed more efficient gliogenesis, as reflected by a greater percentage of GFAP+/BrdU+ cells than in male rats (# p<0.05 ANOVA sex effect: F (1,16) = 6.48,). (E) PRS reduced the total number of BrdU+/NeuN+ cells in male rats (* p<0.05, ANOVA+Newman-Keul's post-hoc test), with no effect in female rats. (F) PRS had no effect on astroglial differentiation; female rats, independent of group, showed an increase in the total number of newly-formed astroglial cells (# p<0.05, ANOVA sex effect: F (1,16) = 4,53). Bars represent means±SEM (n = 5 rats per group).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2366064&req=5

pone-0002170-g003: Hippocampal neurogenesis and gliogenesis in control and PRS rats.Representative confocal laser scanning microscope image showing cells double-labeled for BrdU (red nuclear staining) and the neuronal marker NeuN (green nuclear staining) (A), and cells double-labeled for BrdU and the glial marker GFAP (green cytoplasmic staining) (B). DG: dentate gyrus; GCL: granular cell layer; arrows: double labeled cells. Scale bars-20 µm. (C,D) PRS did not affect the percentage of NeuN+/BrdU+ cells or the percentage of GFAP+/BrdU+ cells within the total population of BrdU+ cells in male and female rats. It is worth noting, however, that both control and PRS female rats showed more efficient gliogenesis, as reflected by a greater percentage of GFAP+/BrdU+ cells than in male rats (# p<0.05 ANOVA sex effect: F (1,16) = 6.48,). (E) PRS reduced the total number of BrdU+/NeuN+ cells in male rats (* p<0.05, ANOVA+Newman-Keul's post-hoc test), with no effect in female rats. (F) PRS had no effect on astroglial differentiation; female rats, independent of group, showed an increase in the total number of newly-formed astroglial cells (# p<0.05, ANOVA sex effect: F (1,16) = 4,53). Bars represent means±SEM (n = 5 rats per group).
Mentions: Newly-formed neurons and astrocytes were identified by double BrdU/NeuN or BrdU/GFAP immunolabeling (Fig. 3A,B). In male rats, PRS reduced the total number of BrdU+/NeuN+ cells (Fig. 3E), but did not change the percentage of NeuN+ cells within the total population of BrdU+ cells (Fig. 3C). Thus, the reduction in newly-formed neurons did not reflect an effect of PRS on cell differentiation, but was secondary to the overall reduction in BrdU+ cells. PRS did not change the number of NeuN+/BrdU+ cells in female rats (Fig. 3C,E), or the number of GFAP+/BrdU+ cells in either male or female rats (Fig. 3D,F). It is worth noting, however, that both control and PRS female rats showed more efficient gliogenesis, as reflected by a greater number and percentage of GFAP+/BrdU+ cells than in male rats (Fig. 3D,F).

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