Hippocampal cytogenesis and spatial learning in senile rats exposed to chronic variable stress: effects of previous early life exposure to mild stress.

Fernando Jauregui-Huerta,Pamela Hernandez-Carrillo,Griselda Yañez-Delgadillo,Limei Zhang,Joaquín García-Estrada,Sonia Luquín

doi:10.3389/fnagi.2015.00159

Abstract

In this study, we exposed adult rats to chronic variable stress (CVS) and tested the hypothesis that previous early-life exposure to stress changes the manner in which older subjects respond to aversive conditions. To this end, we analyzed the cytogenic changes in the hippocampus and hippocampal-dependent spatial learning performance. The experiments were performed on 18-month-old male rats divided into four groups as follows: Control (old rats under standard laboratory conditions), Early-life stress (ELS; old rats who were exposed to environmental noise from postnatal days, PNDs 21–35), CVS + ELS (old rats exposed to a chronic stress protocol who were previously exposed to the early-life noise stress) and CVS (old rats who were exposed only to the chronic stress protocol). The Morris Water Maze (MWM) was employed to evaluate the spatial learning abilities of the rats at the end of the experiment. Immunohistochemistry against 5′Bromodeoxyuridine (BrdU) and glial fibrillar acidic protein (GFAP) was also conducted in the DG, CA1, CA2 and CA3 regions of the hippocampus. We confocally analyzed the cytogenic (BrdU-labeled cells) and astrogenic (BrdU + GFAP-labeled cells) changes produced by these conditions. Using this procedure, we found that stress diminished the total number of BrdU+ cells over the main proliferative area of the hippocampus (i.e., the dentate gyrus, DG) but increased the astrocyte phenotypes (GFAP + BrdU). The depleted BrdU+ cells were restored when the senile rats also experienced stress at the early stages of life. The MWM assessment demonstrated that stress also impairs the ability of the rats to learn the task. This impairment was not present when the stressful experience was preceded by the early-life exposure. Thus, our results support the idea that previous exposure to mild stressing agents may have beneficial effects on aged subjects.

Highlights

Aging and stress are conditions that compromise the adaptive capabilities of all organisms
Tukey Post hoc analysis revealed that senile rats exposed to chronic variable stress (CVS) took a longer time to reach the platform than did those of the other three groups
No differences were found from trial 5–8, indicating that the CVS rats completed the training under the normal parameters

Summary

Introduction

Aging and stress are conditions that compromise the adaptive capabilities of all organisms. The hippocampus is a well-described limbic region that serves as the physical background for the acquisition/consolidation of spatial memory (O’Keefe and Dostrovsky, 1971) It conserves its cytogenic capabilities for practically all of the neural lineages (Eriksson et al, 1998). Studies on deregulated stress responses and pathological aging have described cytological alterations and memory impairments involving the hippocampal formation (Gould and Tanapat, 1999; Karten et al, 2005; Dranovsky and Hen, 2006; Thuret et al, 2009). Studies on neurogenesis have demonstrated that the proliferative rates may vary in two possible ways: (i) inhibiting the proliferation, survival or differentiation of specific lineages; or (ii) stimulating one or more of those parameters. The results of these studies suggest that the inhibitory/stimulatory effects of stress depend on a series of factors, including the subject’s age, cellular lineage, type and history of stress, etc. (Karten et al, 2005; Dranovsky and Hen, 2006; Thomas et al, 2007)

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Conclusion