Chronic juvenile stress produces corticolimbic dendritic architectural remodeling and modulates emotional behavior in male and female rats

Abstract

Nearly 12% of US children are exposed to intense adverse experiences. Research has demonstrated that these experiences can negatively impact adult health, often resulting in psychopathology. Less attention, however, is given to the impact of childhood adverse experiences on childhood health and wellbeing. Using a rodent model of chronic juvenile stress (restraint 6h daily from postnatal day 20–41), we report that chronic stress has significant immediate morbidities in both males and females during this developmental window. Specifically, we demonstrate that chronic juvenile stress produces depressive-like behavior and significant neuronal remodeling of brain regions likely involved in these behavioral alterations: the hippocampus, prefrontal cortex and amygdala. Chronically stressed males and females exhibit anhedonia, increased locomotion when exposed to novelty, and altered coping strategies when exposed to acute stress. Coincident with these behavioral changes, we report simplification of dendrites in the hippocampus and prefrontal cortex and concurrent hypertrophy of dendrites in the amygdala. Taken together, these results demonstrate that chronically stressed juveniles exhibit aberrant behavioral responses to acute challenges that occur in conjunction with stress-induced remodeling of brain regions intimately involved in regulating emotionality and stress reactivity. Further, the absence of sex differences in our reported stress responses, likely speaks to the decreased sensitivity of immature HPA regulating brain regions to sex hormones.

The bed nucleus of stria terminalis and the amygdala as targets of antenatal glucocorticoids: implications for fear and anxiety responses

“…While stress effects in the BNST morphology seem more similar, since different types of stress induce a general hypertrophy of dendrites in the neurons of this brain region (Pego et al 2008;Vyas et al 2003), the effects of stress in the amygdala are less concordant to our present observation of dendritic atrophy. Whereas chronic juvenile stress leads to a general hypertrophy of amygdalar dendrites (Eiland et al 2011), others failed to find any significant change in dendritic structure after stress exposure in adulthood (Pego et al 2008) and others have shown remarkably divergent changes in amygdalar neurons following different types of stress (Vyas et al 2003;Vyas et al 2002).…”

Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex

“…Both chronically stressed males and females exhibited anhedonia, increased locomotion when exposed to novelty, and altered coping strategies when exposed to acute stress. Chronic stress produced shrinkage of dendrites in the hippocampus and PFC and concurrent hypertrophy of dendrites in the amygdala, with a trend for males to show more robust responses than females (Eiland et al, 2012).…”

“…Demonstration of this was accomplished using a rodent model of chronic restraint stress in juvenile rats daily from postnatal days 20 to 41 (Eiland et al, 2012). Chronic stress produced depressivelike behavior and significant neuronal remodeling of brain regions likely involved in these behavioral alterations: the hippocampus, PFC, and amygdala.…”

Differential neuronal changes in medial prefrontal cortex, basolateral amygdala and nucleus accumbens after postweaning social isolation

“…Neurochemically, altered DA levels have been reported in patients and animal models of depression and schizophrenia (Reynolds 1983;Kapur and Mann 1992;Yadid et al 2001;Dunlop and Nemeroff 2007;Heinz and Schlagenhauf 2010;Niwa et al 2010). Anatomically, in stress-induced depressive animals, changes of neuronal morphology in the mesocorticolimbic system are noted (Shansky and Morrison 2009;Eiland et al 2011). In the BLA, the pyramidal neurons develop exuberant dendritic arbors in response to stress (Vyas et al 2002).…”