Chronic stress selectively reduces hippocampal volume in rats: a longitudinal magnetic resonance imaging study

Abstract

The notion of uncontrollable stress causing reduced hippocampal size remains controversial in the posttraumatic stress disorder literature because human studies cannot discern the causality of effect. Here, we addressed this issue by employing structural magnetic resonance imaging in rats to measure the hippocampus and other brain regions before and after stress. Chronic restraint stress produced approximately 3% reduction in hippocampal volume, which was not observed in control rats. This decrease was not signficantly correlated with baseline hippocampal volume or body weight. Total forebrain volume and the sizes of the other brain regions and adrenal glands were all unaffected by stress. This longitudinal, within-subjects design study provides direct evidence that the hippocampus is differentially vulnerable and sensitive to chronic stress.

Chronic restraint stress in adolescence differentially influences hypothalamic‐pituitary‐adrenal axis function and adult hippocampal neurogenesis in male and female rats

“…Interestingly, exposure to chronic stress during adulthood can lead to a reduction in hippocampal volume if the stress is severe and prolonged enough [(Pham et al, 2003;for review, see Sapolsky (2000)]. For example, using structural magnetic resonance imaging, chronic restraint stress decreases hippocampal volume by 3% in adult male rats (Lee et al, 2009). Thus, the ability of chronic stress to decrease hippocampal volume is dependent on a number of variables including developmental time of exposure, amount of stress and stressor type.…”

Dorsal hippocampal lesions boost performance in the rat sequential reaction time task

“…Here, further research is needed to address the question of comparability between histological and MRI lesion quantification. We chose MRI scans for analyzing lesion extent, because (a) hippocampal damage can be directly measured in the living animal, (b) the brains are not affected by perfusion, brain removal, cutting, and staining and (c) the method has been used by other researchers to validate hippocampal lesions (Lee et al, 2009). On the other hand, it has to be mentioned that (a) the histological analyses are more precise-i.e., the contours, especially of the hippocampus, are better visible histologically-and (b) the injection tracts appear clearly bigger in the MRI scans, due to susceptibility artifacts around the needle tracts (see images of the sham operated animal in Fig.…”

“…During scanning, rats were anesthetized with Isofloran (Baxter GmbH, Unterschleibheim, Germany). For lesion validation we used images with the following parameters (similar to Lee et al, 2009): repetition time (TR) 5 3,000 ls; echo time (TE) 5 31 ls; number of slices 5 17; slice thickness 5 0.7 mm; field of view (FoV) 5 40 3 40 mm 2 ; matrix 5 320 3 320; final spatial resolution 5 0.125 3 0.125 3 0.7 mm 2 . The first coronal slices started from approximately 28.0 mm from bregma and ended at approximately 12.27 according to the atlas by Paxinos and Watson (2007).…”

Stress effects on the hippocampus: a critical review

“…In particular, and with significant clinical implications, human brain imaging studies have reported that PTSD patients had smaller hippocampal volume, which correlated with deficits in verbal memory (e.g., Bremner et al 1995). Although a subsequent monozygotic twin study has suggested that reduced hippocampal volume is a predisposing factor for the development of PTSD following trauma (Gilbertson et al 2002), a recent longitudinal MRI study in rats demonstrated that chronic restraint stress does cause a reduction in hippocampal volume from the prestress size (Lee et al 2009). These effects are likely mediated by stress effects on neuronal morphology and/or neurogenesis in the hippocampus.…”