Environmental Enrichment during Gestation Improves Behavior Consequences and Synaptic Plasticity in Hippocampus of Prenatal-Stressed Offspring Rats

Abstract

Prenatal stress can result in various behavior deficits in offspring. Here we tested the effects of environmental enrichment during gestation used as a preventive strategy on the behavior deficits of prenatal-stressed offspring rats as well as the underlying structure basis. We compared the effect size of environmental enrichment during gestation on prenatal-stressed offspring to that of environmental enrichment after weaning. Our results showed that environmental enrichment during gestation partially prevented anxiety and the damage in learning and memory in prenatal-stressed offspring as evaluated by elevated plus-maze test and Morris water maze test. At the same time, environmental enrichment during gestation inhibited the decrease in spine density of CA1 and dentate gyrus neurons and preserved the expression of synaptophysin and glucocorticoid receptors (GRs) in the hippocampus of prenatal-stressed offspring. There was no significant difference in offspring behavior between 7-day environmental enrichment during gestation and 14-day offspring environmental enrichment after weaning. These data suggest that environmental enrichment during gestation effectively prevented the behavior deficits and the abnormal synapse structures in prenatal-stressed offspring, and that it can be used as an efficient preventive strategy against prenatal stresses.

Environmental enrichment mitigates the sex-specific effects of gestational inflammation on social engagement and the hypothalamic pituitary adrenal axis-feedback system

“…There is also a report that EE counteracts the decreased social exploration and latency that accompanies prenatal valproic acid exposure (Schneider et al, 2006), which attenuates proinflammatory cytokines and reactive oxygen species (Cardinale et al, 2010). However, to-date, studies evaluating the effects of EE following earlylife insults have focused on maternal separation (Francis et al, 2002;Vivinetto et al, 2013) and prenatal stressors such as restraint (Li et al, 2012;Morley-Fletcher et al, 2003) or early exposure to drugs of abuse/misuse (i.e., nicotine; Mychasiuk et al, 2014), but not MIA.…”

Environmental Intervention as a Therapy for Adverse Programming by Ancestral Stress

“…For example, exposing rodents to an enriched environment (EE) with rich social and sensorimotor stimulation decreased anxiety-like behaviours in an elevated plus maze11121314, improved sensorimotor skills1516 and led to larger cell proliferation and neuronal density17 along with increased expression of brain-derived neurotrophic factor (BDNF)1819. In prenatally stressed F1 offspring, EE decreases anxiety-like and fear behaviours14, improves social behaviour20, restores dendritic and synaptic morphology2122 and rescues density of glucocorticoid receptors23. Here we aim to determine if EE represents an effective therapy for the endocrine and behavioural consequences of epigenetically inherited manifestations of transgenerational stress in rats.…”

Handling has an anxiolytic effect that is not affected by the inhibition of the protein kinase C pathway in adult prenatal undernourished male rat offspring

“…Hence, neonatal handling followed by physical EE may restore cognitive functions through PKC signaling. Actually, EE inhibited the decrease in spine densities of the hippocampal CA1 neurons concomitantly with a partial reduction of anxiety and damage in learning and memory of prenatal‐stressed offspring in rats . Additionally, although restraint stress in adult rats causes the reduction of distal apical dendritic spine density in layer II/III pyramidal neurons in PFC in addition to working memory impairment, these are rescued by PKC inhibition through subcutaneous injection of chelerythrine .…”

“…Actually, EE inhibited the decrease in spine densities of the hippocampal CA1 neurons concomitantly with a partial reduction of anxiety and damage in learning and memory of prenatal-stressed offspring in rats. 31 Additionally, although restraint stress in adult rats causes the reduction of distal apical dendritic spine density in layer II/III pyramidal neurons in PFC in addition to working memory impairment, these are rescued by PKC inhibition through subcutaneous injection of chelerythrine. 32 Conversely, major substrates of PKC, for example, myristoylated alanine-rich C kinase substrate and neurogranin, have a role in pre-and postsynaptic regulation of neurotransmitter release and synaptic plasticity.…”