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Opposite effects of early maternal deprivation on neurogenesis in male versus female rats.

Oomen CA, Girardi CE, Cahyadi R, Verbeek EC, Krugers H, Joëls M, Lucassen PJ - PLoS ONE (2009)

Bottom Line: Neurogenesis was significantly increased in male but decreased in female offspring after MD.The MD induced sex-specific effects on neurogenesis cannot be explained by differences in maternal care.It is tempting to speculate that a reduced level of neurogenesis, secondary to early stress exposure, may contribute to maladaptation of the HPA axis and possibly to the increased vulnerability of women to stress-related disorders.

View Article: PubMed Central - PubMed

Affiliation: SILS Centre for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Major depression is more prevalent in women than in men. The underlying neurobiological mechanisms are not well understood, but recent data shows that hippocampal volume reductions in depressed women occur only when depression is preceded by an early life stressor. This underlines the potential importance of early life stress, at least in women, for the vulnerability to develop depression. Perinatal stress exposure in rodents affects critical periods of brain development that persistently alter structural, emotional and neuroendocrine parameters in adult offspring. Moreover, stress inhibits adult hippocampal neurogenesis, a form of structural plasticity that has been implicated a.o. in antidepressant action and is highly abundant early postnatally. We here tested the hypothesis that early life stress differentially affects hippocampal structural plasticity in female versus male offspring.

Principal findings: We show that 24 h of maternal deprivation (MD) at PND3 affects hippocampal structural plasticity at PND21 in a sex-dependent manner. Neurogenesis was significantly increased in male but decreased in female offspring after MD. Since no other structural changes were found in granule cell layer volume, newborn cell survival or proliferation rate, astrocyte number or gliogenesis, this indicates that MD elicits specific changes in subsets of differentiating cells and differentially affects immature neurons. The MD induced sex-specific effects on neurogenesis cannot be explained by differences in maternal care.

Conclusions: Our data shows that early environment has a critical influence on establishing sex differences in neural plasticity and supports the concept that the setpoint for neurogenesis may be determined during perinatal life. It is tempting to speculate that a reduced level of neurogenesis, secondary to early stress exposure, may contribute to maladaptation of the HPA axis and possibly to the increased vulnerability of women to stress-related disorders.

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Dentate gyrus cell proliferation (Ki-67) on PND21.A. In males, MD affected dentate cell proliferation rate at PND21 (F(3,28) = 3,2, p = 0.043). Post-hoc analysis revealed a decrease in MD-glucose injected animals (p<0.05). B. In females, there was no effect of treatment (F(3,28) = 0.41 p = 0.75), although a significant lower number of Ki-67 positive cells was found in females when compared to males (F(1,56) = 8.56; p = 0.005).
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pone-0003675-g004: Dentate gyrus cell proliferation (Ki-67) on PND21.A. In males, MD affected dentate cell proliferation rate at PND21 (F(3,28) = 3,2, p = 0.043). Post-hoc analysis revealed a decrease in MD-glucose injected animals (p<0.05). B. In females, there was no effect of treatment (F(3,28) = 0.41 p = 0.75), although a significant lower number of Ki-67 positive cells was found in females when compared to males (F(1,56) = 8.56; p = 0.005).

Mentions: A two-factor ANOVA revealed no main effect of treatment on proliferation (F(3,56) = 0.72; p = 0.55) but a significant effect of sex (F(1,56) = 8.56; p = 0.005) and a significant interaction (sex×treatment) was found, indicating that the effects of MD are different in males than in females (F(3,56) = 2.88; p = 0.045). Females have overall lower numbers of Ki-67 positive cells. A one-way ANOVA per sex revealed that MD affected dentate cell proliferation in males (F(3,28) = 3.2; p = 0.043) but not in females (F(3,28) = 0.41; p = 0.75, see figure 4). Only the MDG males had significantly decreased numbers of Ki-67 positive cells (post-hoc comparison, p<0.05).


Opposite effects of early maternal deprivation on neurogenesis in male versus female rats.

Oomen CA, Girardi CE, Cahyadi R, Verbeek EC, Krugers H, Joëls M, Lucassen PJ - PLoS ONE (2009)

Dentate gyrus cell proliferation (Ki-67) on PND21.A. In males, MD affected dentate cell proliferation rate at PND21 (F(3,28) = 3,2, p = 0.043). Post-hoc analysis revealed a decrease in MD-glucose injected animals (p<0.05). B. In females, there was no effect of treatment (F(3,28) = 0.41 p = 0.75), although a significant lower number of Ki-67 positive cells was found in females when compared to males (F(1,56) = 8.56; p = 0.005).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2629844&req=5

pone-0003675-g004: Dentate gyrus cell proliferation (Ki-67) on PND21.A. In males, MD affected dentate cell proliferation rate at PND21 (F(3,28) = 3,2, p = 0.043). Post-hoc analysis revealed a decrease in MD-glucose injected animals (p<0.05). B. In females, there was no effect of treatment (F(3,28) = 0.41 p = 0.75), although a significant lower number of Ki-67 positive cells was found in females when compared to males (F(1,56) = 8.56; p = 0.005).
Mentions: A two-factor ANOVA revealed no main effect of treatment on proliferation (F(3,56) = 0.72; p = 0.55) but a significant effect of sex (F(1,56) = 8.56; p = 0.005) and a significant interaction (sex×treatment) was found, indicating that the effects of MD are different in males than in females (F(3,56) = 2.88; p = 0.045). Females have overall lower numbers of Ki-67 positive cells. A one-way ANOVA per sex revealed that MD affected dentate cell proliferation in males (F(3,28) = 3.2; p = 0.043) but not in females (F(3,28) = 0.41; p = 0.75, see figure 4). Only the MDG males had significantly decreased numbers of Ki-67 positive cells (post-hoc comparison, p<0.05).

Bottom Line: Neurogenesis was significantly increased in male but decreased in female offspring after MD.The MD induced sex-specific effects on neurogenesis cannot be explained by differences in maternal care.It is tempting to speculate that a reduced level of neurogenesis, secondary to early stress exposure, may contribute to maladaptation of the HPA axis and possibly to the increased vulnerability of women to stress-related disorders.

View Article: PubMed Central - PubMed

Affiliation: SILS Centre for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Major depression is more prevalent in women than in men. The underlying neurobiological mechanisms are not well understood, but recent data shows that hippocampal volume reductions in depressed women occur only when depression is preceded by an early life stressor. This underlines the potential importance of early life stress, at least in women, for the vulnerability to develop depression. Perinatal stress exposure in rodents affects critical periods of brain development that persistently alter structural, emotional and neuroendocrine parameters in adult offspring. Moreover, stress inhibits adult hippocampal neurogenesis, a form of structural plasticity that has been implicated a.o. in antidepressant action and is highly abundant early postnatally. We here tested the hypothesis that early life stress differentially affects hippocampal structural plasticity in female versus male offspring.

Principal findings: We show that 24 h of maternal deprivation (MD) at PND3 affects hippocampal structural plasticity at PND21 in a sex-dependent manner. Neurogenesis was significantly increased in male but decreased in female offspring after MD. Since no other structural changes were found in granule cell layer volume, newborn cell survival or proliferation rate, astrocyte number or gliogenesis, this indicates that MD elicits specific changes in subsets of differentiating cells and differentially affects immature neurons. The MD induced sex-specific effects on neurogenesis cannot be explained by differences in maternal care.

Conclusions: Our data shows that early environment has a critical influence on establishing sex differences in neural plasticity and supports the concept that the setpoint for neurogenesis may be determined during perinatal life. It is tempting to speculate that a reduced level of neurogenesis, secondary to early stress exposure, may contribute to maladaptation of the HPA axis and possibly to the increased vulnerability of women to stress-related disorders.

Show MeSH
Related in: MedlinePlus