Environmental enrichment rescues survival and function of adult-born neurons following early life stress

Abstract

Adverse experiences early in life are associated with the development of psychiatric illnesses. The hippocampus is likely to play pivotal role in generating these effects: it undergoes significant development during childhood and is extremely reactive to stress. In rodent models, stress in the prepubertal period impairs adult hippocampal neurogenesis (AHN) and behaviours which rely on this process. In normal adult animals, environmental enrichment (EE) is a potent promoter of AHN and hippocampal function. Whether exposure to EE during adolescence can restore normal hippocampal function and AHN following pre-pubertal stress (PPS) is unknown. We investigated EE as a treatment for reduced AHN and hippocampal function following PPS in a rodent model. Stress was administered between post-natal days (PND) 25-27, EE from PND35 to early adulthood, when behavioural testing and assessment of AHN took place. PPS enhanced fear reactions to a CS following a trace fear protocol and reduced the survival of 4-week-old adult-born neurons throughout the adult hippocampus. Furthermore, we show that fewer adult-born neurons were active during recall of the CS stimulus following PPS. All effects were reversed by EE. Our results demonstrate lasting effects of PPS on the hippocampus and highlight the utility of EE during adolescence for restoring normal hippocampal function. EE during adolescence is a promising method of enhancing impaired hippocampal function resulting from early life stress, and due to multiple benefits (low cost, few side effects, widespread availability), should be more thoroughly explored as a treatment option in human sufferers of childhood adversity.

A Baldwin interpretation of adult hippocampal neurogenesis: from functional relevance to physiopathology

“…For example fluoxetine treatment for the first 3 weeks of life normalizes DHN levels in adolescent mice previously exposed to PreS [204], and neonatal handling prevents PreS-induced decrease in AHN [205] and memory function [206] most probably through normalization of the HPA axis activity [207,208]. On the same line, physical activity during adolescence can prevent the occurrence of spatial memory deficits in rats previously exposed to PreS [209] and EE starting in adolescence prevents the enhanced fear and decreased AHN observed in animals exposed to prepubertal stress [210].…”

Early life adversity as a risk factor for cognitive impairment and Alzheimer’s disease

“…Although the programs of environmental enrichment vary among laboratories, they typically involve the introduction of running wheels, toys, and larger cages. Environmental enrichment has shown beneficial effects in preventing ELA-induced cognitive impairment in several studies [ 187 , 188 ]. Compared to maternally deprived controls, animals treated with early-life environmental enrichment (from PND 21 to 81) exhibited higher hippocampal expression of BDNF and cognitive improvements in adulthood [ 189 ].…”

“…Compared to maternally deprived controls, animals treated with early-life environmental enrichment (from PND 21 to 81) exhibited higher hippocampal expression of BDNF and cognitive improvements in adulthood [ 189 ]. Early environmental enrichment also preserved normal AHN and hippocampal-dependent functions [ 188 ]. More importantly, even short-term early environmental enrichment (from PND 22 to 34) can mitigate the adverse consequences of ELA, as evidenced by the retention of long-term potentiation and improved cognitive performance [ 190 ].…”

Overlapping brain correlates of superior cognition among children at genetic risk for Alzheimer’s disease and/or major depressive disorder

“…For instance, child maltreatment is linked to epigenetic changes in oxytocin function, which, in turn, trigger structural and functional brain alterations relevant to reward and external attention processes 80 . Conversely, both rodent and human (adoption) studies indicate that child and adolescent exposure to enriched and emotionally responsive environments can reverse the sequelae of prior ELAs (e.g., restored adult hippocampal neurogenesis, reductions in stress reactivity and biological ageing 64 , 65 , 67 , 81 ). Consequently, the neurobiological mechanisms through which enriched social environments may compensate for the damage inflicted by earlier exposure to harsher milieus, as well as the potential age-specificity of any detected pathways would be certainly worth exploring in the future.…”