26 research outputs found
Relevance of Stress and Female Sex Hormones for Emotion and Cognition
There are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are predominantly based on male animals. The strongest argument for not using female rodents is their estrous cycle and the fluctuating sex hormones per phase which multiplies the number of animals to be tested. Here, we will discuss studies focused on sex differences in emotionality and cognitive abilities in experimental conditions with and without stress. First, female sex hormones such as estrogens and progesterone affect emotions and cognition, contributing to sex differences in behavior. Second, females respond differently to stress than males which might be related to the phase of the estrous cycle. For example, female rats and mice express less anxiety than males in a novel environment. Proestrus females are less anxious than females in the other estrous phases. Third, males perform in spatial tasks superior to females. However, while stress impairs spatial memory in males, females improve their spatial abilities, depending on the task and kind of stressor. We conclude that the differences in emotion, cognition and responses to stress between males and females over the different phases of the estrous cycle should be used in animal models for stress-related psychiatric disorders
Forced swimming differentially affects male and female brain corticosteroid receptors
Corticosteroid receptors are key mediators of the neuroendocrine
response to stress. Previously, we have determined the effects of
restraint stress on the regulation of corticosteroid receptor genes in
the brain and pituitary of male and female rats. Significant gender- and
regional-specific regulation of receptor mRNAs was observed. To further
investigate the stressor specificity in the same context, we have
determined glucocorticoid receptor (GR) and mineralocorticoid receptor
(MR) mRNAs following exposure to swimming stress paradigms applied
alone, or in combination with restraint stress. Our data revealed
stressor-specific alterations in GR or MR mRNA levels, which were more
pronounced in males, the gender most affected by swimming stress. No
alterations in GR or MR mRNA levels were detected in the female
hippocampus and hypothalamus upon exposure to swimming paradigms, while
in males the same stressors down-regulated GR mRNA in the hippocampus
(chronic exposure) and up-regulated both genes in the hypothalamus
(acute exposure). In the frontal cortex, acute swimming stress caused a
reciprocal change in GR mRNA levels in the two sexes. The above
difference is not due to circulating ovarian steroids, since ovariectomy
did not change the female pattern of GR gene expression following acute
stress. Our results further showed a hypothalamic-pituitary-adrenal axis
facilitation to a novel superimposed stressor expressed at the level of
limbic corticosteroid receptors: When chronically restrained rats of
both sexes were exposed to acute swimming stress, a reduced GR/MR mRNA
ratio, implying reduced feedback axis sensitivity, was detected in both
the hippocampus and the hypothalamus. In conclusion, our work provides
additional evidence on stressor, gender and region specificity in the
regulation of brain corticosteroid receptors
Long-lasting effects of stress on glucocorticoid receptor gene expression in the rat brain
Stressful stimuli are known to affect glucocorticoid receptor (GR) mRNA
levels in the rat brain. The aim of this study was to examine the
duration of chronic stress-induced changes in GR gene expression in the
male rat hippocampus and cerebellum. By using in situ hybridization
histochemistry, we detected a statistically significant down-regulation
of GR mRNA both in the hippocampus and in the cerebellum of rats
stressed for 8, 10 and 14 days, The same degree of down-regulation could
also be detected in the above brain areas of rats stressed for 14 days
and left undisturbed for 48 h or 8 days after stress. To examine the
effects of subsequent stressors on the expression of down-regulated GR
mRNA in the hippocampus of chronically stressed rats, we determined, by
Northern blotting, GR mRNA levels in the hippocampi of rats stressed for
14 days and subsequently exposed to either short- or long-duration
stressors. The down-regulated levels of GR mRNA remained practically
unaffected when a subsequent new stressor was applied. Our results show
that chronic stress-induced down-regulation of GR mRNA in the rat brain
can be extended for periods longer than the initial/causative stimulus,
irrespective of the presence of a novel stimulus
Effects of gender and stress on the regulation of steroid receptor coactivator-1 expression in the rat brain and pituitary
Steroid/thyroid actions in the brain are exerted through their receptors
which belong to the nuclear receptor superfamily. Transcriptional
transactivation mediated by these receptors depends on recruited
co-activators, among which steroid receptor co-activators (SRCs) seem to
be restricted to the nuclear receptor family. By using Northern and
Western blot analysis we have estimated the mRNA and protein levels,
respectively, of SRC-1 in the brain and pituitary of male and female
rats, under physiological conditions and Following restraint stress.
Under basal conditions, SRC-1 is expressed at higher levels in the
hippocampus and the pituitary of male, compared to female rats. Acute
stress results in decreased, compared to the control, SRC-1 levels in
the hypothalamus of both sexes, in the pituitary and frontal cortex of
male rats, and in increased SRC-1 levels in the hippocampus of female
rats. The observed changes at the mRNA level are supported by analogous
changes at the protein level. The apparent regulation of SRC-1 gene
expression in the nervous system by the endocrine status of the animal,
adds another level of complexity in the mechanism controlling steroid
hormone actions, Furthermore, the variability in SRC-l expression within
the brain provides a means to explain the cell-specificity of steroid
hormone actions in this tissue. (C) 2001 Elsevier Science Ltd. All
rights reserved
Casual discovery of a thoracic tumour showing histological features of undifferentiated pleomorphic sarcoma in a male wistar laboratory rat
Sarcomas are neoplasms of mesenchymal origin, with a predominant cell population mimicking the organization of various soft tissues and/or bones. Previous categorizations also included the possibility of the presence of tissue macrophage-like (histiocytes) neoplasm cells, in a tumour described as malignant fibrous histiocytoma, but this group has been considered as a variety of undifferentiated pleomorphic sarcomas. Although this kind of malignancy is not rare in humans, only few cases have been reported in laboratory animals. We report an unusual single case of spontaneous tumour growth, detected by casual observation, in the left thoracic area of an 18-month-old male laboratory Wistar rat. Both this individual and his ancestors were not exposed to any known carcinogenic substance or radiation, thus suggesting the development of the neoplasm as a spontaneous event. The mass was extracted surgically under general anaesthesia, and slices were examined histologically and immunohistochemically, using photon microscopy. The pathologist reported the presence of a combination of fibroblasts and undifferentiated mesenchymal cells arranged in a storiform pattern. Immunohistochemistry was performed on the tissue using specific antibodies for several proliferation (Ki-67) and differentiation (S-100, CD-34, CD-68, pan-keratin, desmin and smooth muscle actin-SMA) markers. Positive reaction was observed for S-100, Ki-67, CD-68, desmin and SMA (limited) but not for CD-34 or cytokeratin. © 2007 Blackwell Verlag
Ontogeny of intrinsic innervation in the human kidney
We aimed to define, for the first time, the ontogeny of intrarenal
innervation and to assess the distribution and nature of parenchymal
nerves in the human fetal kidney. Our material consisted of
routinely-processed renal tissue sections from 17 human fetuses, six of
20-24 gestational weeks (gw) and 11 of 25-40 gw, and three adults. We
used immunohistochemistry with antibodies to the pan-neural markers
neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100, and
the adrenergic marker tyrosine hydroxylase (TH). NSE-, NF-, S100-, and
PGP9.5-positive nerves, associated with arterial and venous vasculature,
were identified in the renal cortex from 20 gw onwards, and their
density appeared to increase with gestation, reaching adult levels at 28
gw. Most of the intrarenal nerves were TH-positive. Nerve fibers
extended from the corticomedullary region to the outer cortex, reaching
the renal capsule in the 3rd trimester. In detail, NSE-, NF-, S100-,
PGP9.5-, and TH-immunoreactive fibers were observed in close apposition
to the renal artery and its branches, occasionally reaching the afferent
and efferent arteriole (3rd trimester). Nerve fibers were detected in
close apposition to the juxtaglomerular apparatus in the 2nd and 3rd
trimesters. In the renal medulla, NSE-, PGP9.5-, S100-, and TH-positive
nerve fibers were detected close to tubular cells as early as 20 gw.
However, their density gradually decreased during the 3rd trimester, and
they were not observed in the medulla of the adult kidney. In
conclusion, the human fetal kidney appears richly innervated during the
2nd and 3rd trimesters. There is a progressive increase in the density
of parenchymal nerve fibers towards term from the corticomedullary
region to the cortex. Most intrarenal nerves are adrenergic and have a
predominant perivascular distribution, implying that renal innervation
plays an important functional role during intrauterine life
Ontogeny of intrinsic innervation in the human thymus and spleen
The ontogeny of the innervation of human lymphoid organs has not been studied in detail. Our aim was to assess the nature and distribution of parenchymal nerves in human fetal thymus and spleen. We used the peroxidase immunohistochemical technique with antibodies specific to neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100 protein, and tyrosine hydroxylase (TH) and evaluated our results with image analysis. In human fetal thymus, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerves were identified associated with large blood vessels from 18 gestational weeks (gw) onwards, increasing in density during development. Their branches penetrated the septal areas at 20 gw, reaching the cortex and the corticomedullary junction between 20 and 23 gw. Few nerve fibers were seen in the medulla in close association with Hassall's corpuscles. In human fetal spleen, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were localized in the connective tissue surrounding the splenic artery at 18 gw. Perivascular NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were seen extending into the white pulp, mainly in association with the central artery and its branches, increasing in density during gestation. Scattered NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers and endings were localized in the red pulp from 18 gw onward. The predominant perivascular distribution of most parenchymal nerves implies that thymic and splenic innervation may play an important functional role during intrauterine life. © The Histochemical Society, Inc