Abstract
Early life stress can exert detrimental or beneficial effects on neural development and postnatal behavior depending on the timing, duration, strength, and ability to control the stressors. In this study, we utilized a maternal and social deprivation (MSD) model to investigate the effects of early life stress on neural stem cells (NSCs) and neurogenesis in the adult brain. We found that MSD during the stress-hyporesponsive period (SHRP) (early-MSD), when corticosterone secretion is suppressed, increased the size of the NSC population, whereas the same stress beyond the SHRP abrogated these effects. Early-MSD enhanced neurogenesis not only in the dentate gyrus of the hippocampus, one of the classic neurogenic regions, but also in the amygdala. In addition, mice exposed to early-MSD exhibited a reduction in amygdala/hippocampus-dependent fear memory. These results suggest that animals exposed to early life stress during the SHRP have reinforced stress resilience to cope with perceived stressors to maintain a normal homeostatic state.
Highlights
Environmental manipulation during postnatal life predisposes the mammalian brain to altered function and cellular remodeling resulting in behavioral and mood changes
We found that the total number of neurosphere-forming neural stem cells (NSCs) in the subependymal zone (SEZ) was significantly higher in the early-maternal and social deprivation (MSD) mice (3666.4 ± 223.3, mean ± SEM) compared to controls (2589.6 ± 235.7), late-MSD (2053.7 ± 125.0), or extended-MSD (2432.3 ± 378.4) mice (Figure 1B; one-way analysis of variance (ANOVA), F(3,33) = 6.818, p = 0.0011)
We show for the first time that early life stress exhibits distinct effects on the activity of the NSC-neurogenesis system in the adult brain, depending on the timing and duration of the stress
Summary
Environmental manipulation during postnatal life predisposes the mammalian brain to altered function and cellular remodeling resulting in behavioral and mood changes. The postnatal hippocampus and amygdala are the most active regions for the neurodevelopment including serial neurogenesis, cell differentiation, and migration, during the first 2 weeks of life During these periods in rodents, the HPA axis is insensitive to environmental stimuli and this stresshyporesponsive period (SHRP) is thought to be neuroprotective against the stress-induced excessive release of corticosterone during early postnatal development (Levine, 2002; Schmidt et al, 2003; Fodor and Zelena, 2014; Macrì, 2017). A recent finding showed that early life stress induced by limited bedding and nesting paradigm delayed the dentate gyrus development and depletes adult stem cell pool without affecting neurogenesis (Youssef et al, 2019) It remains unclear whether early life stress alters the size of the neural precursor population in SEZ and the adult neurogenesis in brain regions that can predict stress–resilience or vulnerability related to emotion and mood, in addition to the classic neurogenic regions
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