Chronic stress effects on dendritic morphology in medial prefrontal cortex: sex differences and estrogen dependence

Abstract

A growing body of work has documented sex differences in many behavioral, neurochemical, and morphological responses to stress. Chronic stress alters morphology of dendrites in medial prefrontal cortex in male rats. However, potential sex differences in stress-induced morphological changes in medial prefrontal cortex have not been examined. Thus, in Experiment 1 we assessed dendritic morphology in medial prefrontal cortex in male and female rats after chronic stress. Male and female rats underwent either three hours of restraint daily for one week or were left unhandled except for weighing. On the final day of restraint, all rats were euthanized and brains were stained using a Golgi-Cox procedure. Pyramidal neurons in layer II-III of medial prefrontal cortex were drawn in three dimensions, and morphology of apical and basilar arbors was quantified. In males, stress decreased apical dendritic branch number and length, whereas in females, stress increased apical dendritic length. In Experiment 2, we assessed whether estradiol mediates this stress-induced dendritic hypertrophy in females by assessing the effects of restraint stress on female rats that had received either ovariectomy with or without 17-β-estradiol replacement or sham ovariectomy. Brains were processed and neurons reconstructed as described in Experiment 1. Both sham-operated and ovariectomized rats with estradiol implants showed stress-induced increases in apical dendritic material, whereas ovariectomy without estradiol replacement prevented the stress-induced increase. Thus, the stress-induced increase in apical dendritic material in females is estradiol-dependent.

Higher diurnal salivary cortisol levels are related to smaller prefrontal cortex surface area in elderly men and women

“…Our result extends this finding to include both genders and cortisol levels under physiological conditions as compared with levels after pharmacologic suppression. We expected a weaker association between cortisol levels and brain morphology in women than men, based on experimental data (18,30), but this was not supported by our results. Importantly, all women in our sample were older than 55 years and thus were probably postmenopausal.…”

“…High salivary cortisol levels have also been related to a thinner cortex in several PFC regions in healthy men (15), but this has not been tested in women. Importantly, experimental research suggests gender-specific differences in the effects of glucocorticoids on PFC and HC neurons (17,18). Furthermore, a putative association between cortisol levels and HC volume is confounded by small samples (9), coexisting depression (13) or cardiovascular disease (14).…”

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

“…There are sex differences in response to chronic stress in mPFC neurons, in which female rats with intact ovaries or estrogen treatment after ovariectomy showed an expansion of dendrites, whereas males show a chronic stress-induced retraction (Garrett and Wellman, 2009). Refining this in terms of where mPFC neurons project, Shansky showed that female rats fail to show the mPFC dendritic remodeling seen in males after CRS in those neurons that do not project to amygdala.…”

Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex

“…To our knowledge, no study has investigated the effects of stress on infralimbic neuronal architecture in female rats. Nevertheless, a recent study showed higher morphological complexity of pyramidal neurons in the anterior cingulate and prelimbic cortices when adult female rats are exposed to chronic stress (Garrett & Wellman, 2009). Yet, we should bear in mind that the current knowledge of the structural changes in the prefrontal cortex induced by exposure to stress came from studies in adult animals.…”

“…So far, the majority of studies imaging metabolic activation during extinction in rodents have focused on males (mainly adults) (Bruchey, Shumake, & Gonzalez-Lima, 2007;Hefner et al, 2008;Herry & Mons, 2004;Muigg et al, 2008). Yet it is becoming increasingly clear that females differ from males in their morphological and behavioral responses to stress and brain response to various stimuli (Garrett & Wellman, 2009;Maeng, Waddell, & Shors, 2010).…”