A longitudinal study of stress‐induced hippocampal volume changes in mice that are susceptible or resilient to chronic social defeat

Abstract

Hippocampal shrinkage is a commonly found neuroanatomical change in stress-related mood disorders such as depression and post-traumatic stress disorders (PTSD). Since the onset and severity of these disorders have been found to be closely related to stressful life events, and as stress alone has been shown to reduce hippocampal volume in animal studies, vulnerability to mood disorders may be related to a susceptibility to stress-induced hippocampal shrinkage. However, a smaller hippocampal volume before stress exposure has also been suggested to confer vulnerability of stressed individuals to PTSD or depression. In this study, we examined the contribution of either innate hippocampal volume differences or hippocampal susceptibility to stress-induced shrinkage to the formation of stress-related psychopathology using longitudinal MRI measurements of hippocampal volume in inbred C57 mice before and after chronic social defeat stress. We found that only half of the stressed C57 mice were susceptible to stress and developed psychopathological behaviors such as social avoidance. The other half was resilient to stress and exhibited no social avoidance. Before exposure to stress, we observed a positive correlation between hippocampal volume and social avoidance. After chronic social defeat stress, we found significant increases in left hippocampal volume in resilient and nonstressed control mice. Intriguingly, this increase in hippocampal volume was not found in susceptible mice, suggesting an arrestment of hippocampal growth in these mice. Our findings suggest that both a susceptibility to stress-induced hippocampal volume changes and a larger hippocampus before stress exposure confer vulnerability to psychopathology after chronic stress.

Relationship Between Behaviors and Catecholamine Content in Prefrontal Cortex and Hippocampus of Chronically Stressed Rats

“…In addition, levels of NA are elevated in depressed patients [25]. An important result in this work is that CRS induce significant increase of hippocampal NA concentration (p<0.01), which confirm that the hippocampus is particularly sensitive to chronic stress [26], [27]. In a study by Leonard [25], significant negative correlations between aggressive responses and the DA synthesis capacity were observed especially in the midbrain.…”

“…The prefrontal cortex connects with regions of the brain that govern emotional behavior and stress responses, such as the amygdala, hypothalamus, and midbrain periaqueductal gray [1]. In addition, the hippocampus is a region that plays a crucial role in learning and memory and is an area also particularly susceptible to chronic stress [2], [3]. The monoaminergic-sympathetic nervous systems play important roles in maintaining homeostasis by inducing various physiological and behavioral changes [4].…”

Chronic psychosocial stress in mice leads to changes in brain functional connectivity and metabolite levels comparable to human depression

“…Chronic immobilization stress in rat was without effect on hippocampal volume (Henckens et al, 2015). In mice that were susceptible to CSD in terms of decreased social avoidance, there was no increase in hippocampal volume post-versus pre-CSD, whereas there was an increase in hippocampal volume in control and resilient CSD mice (Tse et al, 2014). An ex vivo MRI study reported that hippocampal volume correlated positively with social avoidance score in CSD mice (Anacker et al, 2016).…”

Nociception, Pain, Negative Moods, and Behavior Selection

“…Decreases in hippocampus and amygdala volumes have also been described in post-traumatic stress (PTSD) (Chao et al, 2013; Chao et al, 2014; Gilbertson et al, 2002; Starcevic et al, 2014), and white matter microstructural predispositions in PTSD indicate that such structural differences reflect long-term vulnerability (Sekiguchi et al, 2014), as also observed for chronic back pain (Mansour et al, 2013). In humans, amygdala response properties seem to indicate risk for developing PTSD (McLaughlin et al, 2014), and in rodents, susceptibility to stress response is dependent on hippocampal volume and functional processing (Nalloor et al, 2014; Tse et al, 2014). Chronic tinnitus, a persistent unpleasant sensation of ringing or buzzing in the ear, is also now characterized as a dysregulation of the limbic network, mainly due to hyperactivity of the ventral striatum coupled with decreased grey matter in the medial prefrontal cortex (Leaver et al, 2011).…”