Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

Abstract

Studies show that sex plays a role in stress-related depression, with women experiencing a higher vulnerability to its effect. Two major targets of antidepressants are brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element–binding protein (CREB). The aim of this study was to investigate the levels of CREB, phosphorylation of CREB (pCREB), and BDNF in stress-related brain regions of male and female rats after stress and recovery. CREB and pCREB levels were examined in CA1, CA2, CA3, paraventricular nucleus of the thalamus (PVT), amygdala, anterior cingulate area, dorsal part (ACAd), and infralimbic area of prefrontal cortex (PFC), whereas dentate gyrus (DG) and prelimbic area (PL) of PFC were examined for BDNF levels. Our results demonstrate that levels of CREB and pCREB in male CA1, CA2 and CA3, PVT, amygdala, and ACAd were reduced by stress, whereas the same brain regions of female rats exhibited no change. BDNF levels were decreased by chronic stress in female PL but were increased by acute stress in female DG. BDNF levels in male DG and PL were found not to undergo change in response to stress. Abnormalities in morphology occurred after chronic stress in males but not in females. In all cases, the levels of CREB, pCREB, and BDNF in recovery animals were comparable to the levels of these proteins in control animals. These findings demonstrate a sexual dimorphism in the molecular response to stress and suggest that these differences may have important implications for potential therapeutic treatment of depression.

Differences in Active Avoidance Conditioning in Male and Female Rats with Experimental Anxiety-Depressive Disorder

“…Our fi ndings are consistent with the idea that female hormones that regulate production of corticotrophin-releasing factor can play the key role in hyperactivity of the hypothalamic-pituitary-adrenal axis, while changes in their level determine the severity of the stress reaction and is a risk factor for depression development [15]. Worse learning of experimental females in comparison with experimental males can be associated with higher sensitivity of females to the development of depression-like behavior [14].…”

Transcriptional Control of Monocyte Gene Expression in Post-Traumatic Stress Disorder

“…However, we found that target genes for CREB/ATF were significantly downregulated in women with trauma exposure and PTSD, indicating decreased CREB/ATF signaling in monocytes in the female sample. Sex hormone differences may influence stress effects on CREB and thereby influence the expression of target genes for CREB/ATF [28,29,55]. However, it is also possible that differences in trauma exposure between the male and female control groups contributed to the findings.…”

Exposure to Prenatal Psychobiological Stress Exerts Programming Influences on the Mother and Her Fetus

“…There is a rapidly expanding literature in animal models indicating that there are sexually dimorphic responses to stress and adversity [122,123,124] including and perhaps especially associated with stress during the prenatal period [125,126,127]. In the study of human FHR responses to external stimulation reported above [44], we discovered that female fetuses displayed more mature responses than males at 31 and 36 gestational weeks.…”