Stress and the female brain. The effects of estradiol on the neurobiological reactions to chronic stress.

Affective disorders occur more often in women than in men. Moreover, severe instabilities in plasma estrogen levels in women, occurring postpartum and during the beginning of the perimenopausal period, are typically associated with an increased risk of the emergence of depressive symptoms and anxiety. Additionally, several studies have reported a reduction of the depressive symptoms in peri- and postmenopausal women during treatment with estrogen. Although the effects of estradiol on mood and anxiety are recognized, the exact mechanisms by which these effects are mediated remain unclear. Since there is a strong association between chronic stressful events and affective disorders in human, stress can be used as a valuable tool in animal research to characterize neurobiological mechanisms underlying major depression and/or anxiety disorders. The aim of the current thesis was to elucidate the role of estradiol on stress-related neurobiological mechanisms in female rats and to demonstrate possible protective effects on stress-induced neuronal dysfunction when estradiol was administered in a cyclic manner.

Stress-induced sensitization of the limbic system in ovariectomized rats is partly restored by cyclic 17 beta-estradiol administration

Chronic stress induces neurobiological alterations which have consequences for subsequent stress handling. In the current experiment, ovariectomized rats were subjected daily to a stressor for 21 days. Thereafter, the rats were treated for 21 days with 17 beta-estradiol benzoate (10 mu g/250 g, once every 4 days) or mirtazapine (10 mg/kg, daily). In this way, we were able to evaluate the ability of these compounds to reverse chronic stress-induced changes in the activity of the limbic system. After 21 days of recovery and treatment, the rats were re-exposed to the adverse environment of the initial stressor and perfused 2 h later. Ovariectomized rats displayed increased numbers of c-Fos-positive nuclei, after re-exposure to the stressor, in the paraventricular nucleus of the hypothalamus, dentate gyrus, medial prefrontal cortex and central and medial amygdala. Cyclic estradiol treatment attenuated the sensitization of the paraventricular nucleus and central amygdala. Mirtazapine increased the number of c-Fos-positive nuclei in the central amygdala and dentate gyrus. Long-term transcriptional changes induced by chronic stress were determined with Delta FosB immunoreactivity. The medial prefrontal cortex showed an increased number of Delta FosB-positive nuclei after chronic stress and this was not affected by estradiol or mirtazapine administration during recovery. In conclusion, cyclic estradiol administration reversed chronic stress-induced sensitization in the limbic system, the paraventricular nucleus and central amygdala of female rats, output regions of the limbic system involved in fear responses. Mirtazapine did not achieve this of stress-induced aberrations in the limbic system after 21 days of treatment

Sex differences in stress responses:Focus on ovarian hormones

Women in the reproductive age are more vulnerable to develop affective disorders than men. This difference may attribute to anatomical differences, hormonal influences and environmental factors such as stress. However, the higher prevalence in women normalizes once menopause is established, suggesting that ovarian hormones may play an important role in the development of depression in women. Ovarian hormones such as estrogen can pass the brain-blood barrier and bind to cytoplasmatic estrogen receptor (ER)-alpha and ER-beta in different areas of the limbic system. During stress. estrogen can modulate the behavioral and neurobiological response depending on the concentrations of estrogen. In this review we present evidence for disparate effects of chronic stress on neuroplasticity and brain activity in male and female rats. Furthermore, we will demonstrate that effects of social support on coping with stress can be mimicked by social housing of rats and that this model can be used for identification of underlying neurobiological mechanisms, including behavior, phosphorylation of CREB and ERK1/2, and brain activity changes as measured with fos expression. Using cyclic administration of estrogen in ovariectomized female rats we could specifically address effects of different plasma estrogen levels and antidepressants on stress-induced neuroplasticity and activity changes. In this model we also studied effects of estrogen on recovery after chronic stress. We conclude that the female brain has a different innate strategy to handle stress than the male brain and that female animal models are necessary for studying the underlying mechanisms and options for treatment. (c) 2009 Elsevier Inc. All rights reserved

The language connectome in the left-handed brain: hemispheric (a)symmetries and beyond

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Evaluation of the language profile in children with rolandic epilepsy and developmental dysphasia: Evidence for distinct strengths and weaknesses

Although benign, rolandic epilepsy (RE) or benign childhood epilepsy with centro-temporal spikes is often associated with language impairment. Recently, fronto-rolandic EEG abnormalities have been described in children with developmental dysphasia (DD), suggesting an interaction between language impairment and interictal epileptiform discharges. To investigate if a behavioral-linguistic continuum between RE and DD exists, a clinical prospective study was carried out to evaluate the language profile of 15 children with RE and 22 children with DD. Language skills were assessed using an extensive, standardized test battery. Language was found to be impaired in both study groups, however RE and DD were associated with distinct language impairment profiles. Children with RE had difficulties with sentence comprehension, semantic verbal fluency and auditory short-term memory, which are unrelated to age of epilepsy onset and laterality of epileptic focus. In children with DD, sentence comprehension and verbal fluency were among their relative strengths, whereas sentence and lexical production constituted relative weaknesses.publisher: Elsevier articletitle: Evaluation of the language profile in children with rolandic epilepsy and developmental dysphasia: Evidence for distinct strengths and weaknesses journaltitle: Brain and Language articlelink: http://dx.doi.org/10.1016/j.bandl.2017.03.006 content_type: article copyright: © 2017 Elsevier Inc. All rights reserved.status: publishe

The mis-wired language network in children with developmental language disorder: insights from DTI tractography

This study aims to detect the neural substrate underlying the language impairment in children with developmental language disorder (DLD) using diffusion tensor imaging (DTI) tractography. Deterministic DTI tractography was performed in a group of right-handed children with DLD (N = 17; mean age 10;07 ± 2;01 years) and a typically developing control group matched for age, gender and handedness (N = 22; mean age 11;00 ± 1;11 years) to bilaterally identify the superior longitudinal fascicle, arcuate fascicle, anterior lateral segment and posterior lateral segment (also called dorsal language network) and the middle and inferior longitudinal fascicle, extreme capsule fiber system and uncinate fascicle (also called ventral language network). Language skills were assessed using an extensive, standardized test battery. Differences in language performance, white matter organization and structural lateralization of the language network were statistically analyzed. Children with DLD showed a higher overall volume and higher ADC values for the left-hemispheric language related WM tracts. In addition, in children with DLD, the majority (88%; 7/8) of the studied language related WM tracts did not show a significant left or right lateralization pattern. These structural alterations might underlie the language impairment in children with DLD.status: publishe