Influence of Pre-reproductive Maternal Enrichment on Coping Response to Stress and Expression of c-Fos and Glucocorticoid Receptors in Adolescent Offspring

Abstract

Environmental enrichment (EE) is an experimental setting broadly used for investigating the effects of complex social, cognitive, and sensorimotor stimulations on brain structure and function. Recent studies point out that parental EE experience, even occurring in the pre-reproductive phase, affects neural development and behavioral trajectories of the offspring. In the present study we investigated the influences of pre-reproductive EE of female rats on maternal behavior and adolescent male offspring's coping response to an inescapable stressful situation after chronic social isolation. For this purpose female Wistar rats were housed from weaning to breeding age in enriched or standard environments. Subsequently, all females were mated and housed in standard conditions until offspring weaning. On the first post partum day (ppd 1), mother-pup interactions in undisturbed conditions were recorded. Further, after weaning the male pups were reared for 2 weeks under social isolation or in standard conditions, and then submitted or not to a single-session Forced Swim Test (FST). Offspring's neuronal activation and plastic changes were identified by immunohistochemistry for c-Fos and glucocorticoid receptors (GRs), and assessed by using stereological analysis. The biochemical correlates were measured in the hippocampus, amygdala and cingulate cortex, structures involved in hypothalamic-pituitary-adrenocortical axis regulation. Enriched dams exhibited increased Crouching levels in comparison to standard reared dams. In the offspring of both kinds of dams, social isolation reduced body weight, decreased Immobility, and increased Swimming during FST. Moreover, isolated offspring of enriched dams exhibited higher levels of Climbing in comparison to controls. Interestingly, in the amygdala of both isolated and control offspring of enriched dams we found a lower number of c-Fos immunopositive cells in response to FST and a higher number of GRs in comparison to the offspring of standard dams. These results highlight the profound influence of a stressful condition, such as the social isolation, on the brain of adolescent rats, and underline intergenerational effects of maternal experiences in regulating the offspring response to stress.

Extending the developmental origins of disease model: Impact of preconception stress exposure on offspring neurodevelopment

“…An example is using an enriched environment to attenuate earlier stress exposure. Cutuli and colleagues (2017) demonstrated that exposure to an enriched environment prior to reproduction had neuroprotective effects on the offspring even after exposure to a stressor; adolescent offspring of enriched dams had a more modulated immune response and more climbing behavior in response to the forced swim test, and greater expression of gluccocorticoid receptors in the amygdala, which was comparable to adolescent offspring of dams who were not stress exposed. Testing the timing and dose of an enriched environment on the attenuation of the effects of preconception stress exposure on offspring neurodevelopment is necessary for pursuing a preventive intervention program in humans.…”

Effects of Physical Exercise on Cognitive Functioning and Wellbeing: Biological and Psychological Benefits

“…Interestingly, PE induces modifications that can be passed on to the offspring. In fact, positive maternal experiences can influence the offspring at both behavioral and biochemical levels (see Cutuli et al, 2017 , 2018 ). Preclinical studies also indicated that the effects of maternal exercise during pregnancy can be passed on to offspring (Robinson et al, 2012 ).…”

Coping with Stress During Aging: The Importance of a Resilient Brain

“…Finally, we found that enriched aged rats showed a reduced emotional reactivity to the conflict approach/avoidance and an improvement in decision making in the elevated-zero maze (EZM) test. Recently, pre-reproductive maternal enrichment was reported to influence offspring’s coping response to stress and expression of c-Fos and glucocorticoid receptors (GRs) [ 95 ].…”