Opposite Effects of Early Maternal Deprivation on Neurogenesis in Male versus Female Rats

Abstract

BackgroundMajor 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 FindingsWe 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.ConclusionsOur 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.

Sex-related long-term behavioral and hippocampal cellular alterations after nociceptive stimulation throughout postnatal development in rats

“…One could hypothesize that the abovementioned outcomes of the neonatal stressful event could be preparatory for possible future adverse events. In fact, there is evidence in favor of such hypothesis, stemming from studies in human beings (Boyce and Chesterman, 1990;Edge et al, 2009), squirrel monkeys (reviewed in Parker et al (2006)) and rodents (Champagne et al, 2008;Hays et al, 2012;Oomen et al, 2009). Alterations in multiple pathways in the central nervous system may contribute to alter the behavioral repertoire in adulthood following neonatal nociceptive stimuli.…”

Social stratification, classroom climate, and the behavioral adaptation of kindergarten children

“…Sex differences in social adversity-related neurobiology have also been noted in animals, including opposite effects of stress on memory formation in male vs. female rats (74) and sex differences in the impact of early maternal deprivation on rat hippocampal neurogenesis (75). The sex differences reported here in associations among rank, SES, classroom climate, and adaptive behavior might thus stem in part from the persistent psychological stressors of peer group subordination and sex-linked differences in its neurobiological correlates.…”

Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation

“…This proximity suggests a strong interaction with the vasculature, which is of relevance as it is indeed this population that is particularly sensitive to stress (Heine et al 2005). Also, astrocytes are important as this cell type supports the survival of developing neurons, possess GR, and are affected by some, but not all, types of stress (Czéh et al 2006;Banasr and Duman 2008;Oomen et al 2009). …”

“…Similarly, maternal deprivation (MD) is found to transiently increase numbers of immature (doublecortin [DCX]-positive) neurons in rats at 3 wk of age (Oomen et al 2009), ultimately leading to reduced proliferation throughout the full rostrocaudal axis of the DG, and reduced differentiation in the caudal part of the DG at 10 wk of age (Oomen et al 2009). The evidence presented above suggests that the ELS-induced reduced neurogenic capacity observed later in life might be caused by an increase in neurogenesis during the postnatal phase that might result in depletion of the neurogenic pool.…”