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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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Doublecortin (DCX) -positive neuron numbers on PND21.A significant treatment×sex interaction revealed a differential effect of MD on males versus females (F(3,48) = 8.04; p<0.0001). A. An increase in DCX+ cell number was found in deprived males (F(3,28) = 4.3, p = 0.018; post-hoc: CONU = CONS<MDS = MDG, at least p<0.05) and a decrease in deprived females (F(3,28) = 4.65, p = 0.013; post-hoc: CONU = CONS>MDS = MDG, at least p<0.05) when compared to controls. A significant effect of sex indicates a general lower amount of DCX+ cells in females (F(1,48) = 65.80; p<0.0001).
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pone-0003675-g007: Doublecortin (DCX) -positive neuron numbers on PND21.A significant treatment×sex interaction revealed a differential effect of MD on males versus females (F(3,48) = 8.04; p<0.0001). A. An increase in DCX+ cell number was found in deprived males (F(3,28) = 4.3, p = 0.018; post-hoc: CONU = CONS<MDS = MDG, at least p<0.05) and a decrease in deprived females (F(3,28) = 4.65, p = 0.013; post-hoc: CONU = CONS>MDS = MDG, at least p<0.05) when compared to controls. A significant effect of sex indicates a general lower amount of DCX+ cells in females (F(1,48) = 65.80; p<0.0001).

Mentions: The most prominent effects of MD were observed at PND21 in neurogenesis, as measured by the young neuronal marker doublecortin (DCX; figure 6), A two-factor ANOVA revealed no main effect of treatment (F(7,48) = 1.50; p = 0.23), but an effect of sex, indicating that females have in general less DCX-positive cells (F(1,48) = 65.80; p<0.0001). Interestingly, a significant interaction between sex and treatment was found, indicating that the effects of MD on neurogenesis were different for males than females, (treatment×sex; F(3,48) = 8.04; p<0.0001). A one-way ANOVA in males, revealed a significant increase in the total number of DCX+ cells due to maternal deprivation (F(3,28) = 4.3; p = 0.018; post-hoc LSD: CONU = CONS<MDS = MDG, at least p<0.05, see figure 7A). In females, MD was found to lead to lower total DCX+ cell numbers, (F(3,28) = 4.65; p = 0.013; post-hoc LSD: CONU = CONS>MDS = MDG, at least p<0.05 see figure 7B). When corrected for granular cell layer volume, these effects persisted (data not shown).


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)

Doublecortin (DCX) -positive neuron numbers on PND21.A significant treatment×sex interaction revealed a differential effect of MD on males versus females (F(3,48) = 8.04; p<0.0001). A. An increase in DCX+ cell number was found in deprived males (F(3,28) = 4.3, p = 0.018; post-hoc: CONU = CONS<MDS = MDG, at least p<0.05) and a decrease in deprived females (F(3,28) = 4.65, p = 0.013; post-hoc: CONU = CONS>MDS = MDG, at least p<0.05) when compared to controls. A significant effect of sex indicates a general lower amount of DCX+ cells in females (F(1,48) = 65.80; p<0.0001).
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Related In: Results  -  Collection

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

pone-0003675-g007: Doublecortin (DCX) -positive neuron numbers on PND21.A significant treatment×sex interaction revealed a differential effect of MD on males versus females (F(3,48) = 8.04; p<0.0001). A. An increase in DCX+ cell number was found in deprived males (F(3,28) = 4.3, p = 0.018; post-hoc: CONU = CONS<MDS = MDG, at least p<0.05) and a decrease in deprived females (F(3,28) = 4.65, p = 0.013; post-hoc: CONU = CONS>MDS = MDG, at least p<0.05) when compared to controls. A significant effect of sex indicates a general lower amount of DCX+ cells in females (F(1,48) = 65.80; p<0.0001).
Mentions: The most prominent effects of MD were observed at PND21 in neurogenesis, as measured by the young neuronal marker doublecortin (DCX; figure 6), A two-factor ANOVA revealed no main effect of treatment (F(7,48) = 1.50; p = 0.23), but an effect of sex, indicating that females have in general less DCX-positive cells (F(1,48) = 65.80; p<0.0001). Interestingly, a significant interaction between sex and treatment was found, indicating that the effects of MD on neurogenesis were different for males than females, (treatment×sex; F(3,48) = 8.04; p<0.0001). A one-way ANOVA in males, revealed a significant increase in the total number of DCX+ cells due to maternal deprivation (F(3,28) = 4.3; p = 0.018; post-hoc LSD: CONU = CONS<MDS = MDG, at least p<0.05, see figure 7A). In females, MD was found to lead to lower total DCX+ cell numbers, (F(3,28) = 4.65; p = 0.013; post-hoc LSD: CONU = CONS>MDS = MDG, at least p<0.05 see figure 7B). When corrected for granular cell layer volume, these effects persisted (data not shown).

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