Environmental enrichment protects spatial learning and hippocampal neurons from the long-lasting effects of protein malnutrition early in life.

As early protein malnutrition has a critically long-lasting impact on the hippocampal formation and its role in learning and memory, and environmental enrichment has demonstrated great success in ameliorating functional deficits, here we ask whether exposure to an enriched environment could be employed to prevent spatial memory impairment and neuroanatomical changes in the hippocampus of adult rats maintained on a protein deficient diet during brain development (P0-P35). To elucidate the protective effects of environmental enrichment, we used the Morris water task and neuroanatomical analysis to determine whether changes in spatial memory and number and size of CA1 neurons differed significantly among groups. Protein malnutrition and environmental enrichment during brain development had significant effects on the spatial memory and hippocampal anatomy of adult rats. Malnourished but non-enriched rats (MN) required more time to find the hidden platform than well-nourished but non-enriched rats (WN). Malnourished but enriched rats (ME) performed better than the MN and similarly to the WN rats. There was no difference between well-nourished but non-enriched and enriched rats (WE). Anatomically, fewer CA1 neurons were found in the hippocampus of MN rats than in those of WN rats. However, it was also observed that ME and WN rats retained a similar number of neurons. These results suggest that environmental enrichment during brain development alters cognitive task performance and hippocampal neuroanatomy in a manner that is neuroprotective against malnutrition-induced brain injury. These results could have significant implications for malnourished infants expected to be at risk of disturbed brain development.

Environmental enrichment reverses reduction in glucocorticoid receptor expression in the hippocampus of and improves behavioral responses of anxiety in early malnourished rats.

We compared glucocorticoid receptor (GR) gene expression in the hippocampus of rats subjected to a low protein, "malnourished" diet (M; 6% protein) or a control, "well-nourished" diet (W; 16% protein), exposed to different environmental stimulation (environmental enrichment, E; no enrichment, N) between postnatal day 8 (P8) and P35. Rats were tested on the elevated plus maze (EPM) on P36. Male Wistar rats were split into two groups at birth according to diet (M or W) and subdivided according to environmental stimulation (E or N). GR expression was determined using real-time polymerase chain reaction and GR immunohistochemistry in the hippocampus. Our results showed that MN rats spent more time and made more entries into the open arms of the EPM compared to W rats. On the other hand, ME rats spent a similar percentage of time, and made a similar number of entries, in the open arms as WN rats. Following the EPM test, GR mRNA expression in the hippocampus was different in MN rats compared to W rats; expression was also different between M and ME rats; mRNA and expression of GR receptors in WN rats was similar to that observed in WE rats. These data also show that the effects of malnutrition on risk assessment in the EPM were reversed by E. Early malnutrition may alter GR expression in the hippocampus and environmental enrichment may exert a neuroprotective effect on malnutrition-induced brain injury.

Effects of early protein malnutrition and environmental stimulation on behavioral and biochemical parameters in rats submitted to the elevated plus-maze test.

The objective of this study was to compare the effects of the tactile/handling stimulation (H) and environmental enrichment (EE) in well-nourished (C - 16% of protein) and malnourished (M - 6% of protein) rats tested in the elevated plus-maze (EPM) at 36 and 37 days of age. The results showed higher exploration of the open arms in the EPM in M as compared with C animals, as well as lower index of risk assessment behaviors, and EE, but not H, reversed the alterations produced by malnutrition in the EPM. Biochemical analysis showed higher levels of corticosterone in M when compared with C rats. The non-stimulated animals presented higher levels of polyamines in the hippocampus when compared with the stimulated ones in both diet conditions. It is suggested that both the lower anxiety levels and the lower risk-assessment behaviors in the EPM, as well as the higher levels of corticosterone, can be due to alterations in the activity of the hypothalamic-pituitary-adrenal axis as the result of early protein malnutrition.