Early hippocampal volume loss as a marker of eventual memory deficits caused by repeated stress.

Mohammed Mostafizur Rahman,Charlotte K Callaghan,Christian M Kerskens,Shane M O’Mara,Sumantra Chattarji

doi:10.1038/srep29127

Abstract

Exposure to severe and prolonged stress has detrimental effects on the hippocampus. However, relatively little is known about the gradual changes in hippocampal structure, and its behavioral consequences, over the course of repeated stress. Behavioral analyses during 10 days of chronic stress pointed to a delayed decline in spatial memory, the full impact of which is evident only after the end of stress. In contrast, concurrent volumetric measurements in the same animals revealed significant reduction in hippocampal volumes in stressed animals relative to their unstressed counterparts, as early as the third day of stress. Notably, animals that were behaviorally the worst affected at the end of chronic stress suffered the most pronounced early loss in hippocampal volume. Together, these findings support the view that not only is smaller hippocampal volume linked to stress-induced memory deficits, but it may also act as an early risk factor for the eventual development of cognitive impairments seen in stress-related psychiatric disorders.

Highlights

This study is one of the first attempts to monitor the gradual effects of repeated stress on hippocampal structure and function in the same animal over a period of time
Ten days of chronic immobilization stress had a detrimental effect on hippocampal structure, and its behavioral output
After the end of the chronic stress we found a significant loss in hippocampal volume, as well as impaired spatial memory that depends on the hippocampus

Summary

Introduction

We monitored hippocampal volume in the same animal at three different time points during and after the 10-day chronic stress paradigm: during an early stage on day[3], a later stage on day[7], and after stress on day[11] (Figs 1 and 3). This stress-induced reduction took time to build up as the total hippocampal volume on day[11] was significantly lower compared to that on day[3] in stressed (post hoc Tukey’s multiple comparison test p = 0.0027), but not unstressed, animals (Fig. 3c, left).

Results

Conclusion