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Do early-life events permantently alter behavioral and hormonal responses to stressors.

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Partial reversal of the effect of maternal care on cognitive function through environmental enrichment.

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Maternal care influences hippocampal development in the rat. The offspring of mothers that exhibit increased levels of pup licking/grooming and arched-back nursing (High LG-ABN mothers) show increased hippocampal N-methyl-D-aspartate (NMDA) receptor binding and enhanced hippocampal-dependent spatial learning. In these studies we examined whether environmental enrichment from days 22-70 of life might reverse the effects of low maternal care. Environmental enrichment eliminated the differences between the offspring of High and Low LG-ABN mothers in both Morris water maze learning and object recognition. However, enrichment did not reverse the effect of maternal care on long-term potentiation in the dentate gyrus or on hippocampal NMDA receptor binding. In contrast, peripubertal enrichment did reverse the effects of maternal care on hippocampal a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor binding. These findings provide evidence for the reversal of the effects of reduced maternal investment in early life on cognitive function in adulthood. Such effects might involve compensatory changes associated with peripubertal enrichment. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved


Article
Peripubertal environmental enrichment reverses the effects of maternal care on hippocampal development and glutamate receptor subunit expression.

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Maternal care in the rat influences the development of cognitive function in the offspring through neural systems known to mediate activity-dependent synaptic plasticity. The offspring of mothers that exhibit increased levels of pup licking/grooming (high-LG mothers) show increased hippocampal N-methyl-D-aspartate (NMDA) subunit mRNA expression, enhanced synaptogenesis and improved hippocampal-dependent spatial learning in comparison with animals reared by low-LG mothers. The effects of reduced maternal care on cognitive function are reversed with peripubertal environmental enrichment; however, the neural mechanisms mediating this effect are not known. In these studies we exposed the offspring of high- and low-LG mothers to environmental enrichment from days 22 to 70 of life, and measured the expression of genes encoding for glutamate receptor subunits and synaptophysin expression as a measure of synaptic density. Environmental enrichment reversed the effects of maternal care on synaptic density and this effect was, in turn, associated with a reversal of the effect of maternal care on the NR2A and NR2B subunits of the NMDA receptor, as well as effects on (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits. Finally, direct infusion of an NR2B-specific NMIDA receptor antagonist into the hippocampus eliminated the effects of maternal care on spatial learning/memory in the Morris water maze. These findings suggest that: (1) the effects of maternal care are mediated by changes in NR2B gene expression; and (2) that environmental enrichment reverses the effects of reduced maternal care through the same genomic target, the NR2B gene, and possibly effects on other subunits of the NMIDA and AMPA receptors


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Environmental enrichment reverses the effects of maternal separation on stress reactivity.

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Postnatal maternal separation increases hypothalamic corticotropin-releasing factor (CRF) gene expression and hypothalamic-pituitary-adrenal (HPA) and behavioral responses to stress. We report here that environmental enrichment during the peripubertal period completely reverses the effects of maternal separation on both HPA and behavioral responses to stress, with no effect on CRF mRNA expression. We conclude that environmental enrichment leads to a functional reversal of the effects of maternal separation through compensation for, rather than reversal of, the neural effects of early life adversity


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Effects of neonatal handling on age-ralted impairments associated with the hippocampus.

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Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.

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Maternal care, hippocampal glucocorticoid receptors and hypothalamic-pituitary-adrenal responses to stress.

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