Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the functional impact of local inhibitory gamma-aminobutyric acid (GABA)ergic interneuron population on the cellular and transcriptional activity of parvocellular neurosecretory neurons in the hypothalamic paraventricular nucleus (PVH), we followed the expression of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) genes along with the activation marker c-fos in response to the blockade of GABA-A receptors. First, we analysed the effect of the GABA-A receptor antagonist bicuculline methiodide (BMI) in organotypic cultures of hypothalamic slices. These preparations preserve the cytoarchitecture of CRH-synthesizing cell populations and elements of local interneuronal networks, while remote connections originating from limbic- and brainstem areas are missing. In vitro, BMI resulted in a selective induction of c-Fos immunoreactivity that was localized exclusively to the PVH and upregulated both CRH mRNA and AVP hnRNA levels. Local microinjection of BMI into the paraventricular region of freely moving rats increased the adrenocorticotropin secretion and activated PVH neurons ipsilateral to the injection. c-Fos immunoreactivity was distributed within the PVH and in the perinuclear region, where it appeared in GABAergic and also in non-GABAergic profiles. This treatment induced AVP hnRNA expression in the parvocellular compartment without any reliable stimulation of CRH transcription in the parvocellular- and AVP hnRNA levels in the magnocellular neurons. These results reveal an intrinsic GABAergic mechanism in the PVH microenvironment that by itself, without limbic contribution, impinges a tonic inhibitory influence on the parvocellular CRH neurons in vitro. In vivo, remote inputs are superimposed on the local circuit, allowing differential transcriptional regulation of CRH and AVP genes in the hypophysiotropic neurons.
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PMID:GABAergic control of neuropeptide gene expression in parvocellular neurons of the hypothalamic paraventricular nucleus. 1451 31

Corticosterone regulates both basal and stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity in a negative-feedback fashion. However, the cellular and molecular mechanisms of this negative feedback have yet to be explicitly characterized. By comparing stress-induced c-fos and corticotropin-releasing hormone (CRH) expression in the paraventricular nucleus (PVN), we may be able to determine whether acute glucocorticoid treatment affects the net neural excitatory input to the PVN (represented primarily by c-fos mRNA expression) or directly affects the ability of cells in the PVN to respond to that input (represented primarily by CRH hnRNA expression). In the following studies, we observed the effect of acute glucocorticoid (RU28362) treatment on subsequent HPA axis reactivity by measuring stress-induced plasma hormone concentration [corticosterone and adrenocorticotropic hormone (ACTH)] and gene expression (c-fos and CRH) in the PVN. First, we examined the dose-response relationship between systemically administered RU28362 (1-150 microg/kg, i.p) and suppression of the stress-induced corticosterone response. We then confirmed central nervous system access of the maximally suppressive dose of RU28362 (150 microg/kg) by an ex vivo radioligand binding assay. RU28362 selectively occupied the majority of glucocorticoid receptors in the hippocampus and hypothalamus while having no effect on mineralocorticoid receptors. In separate studies, RU28362 (150 microg/kg) and corticosterone (5 mg/kg) were injected i.p. 1 h before restraint stress. Compared to vehicle-treated controls, rats treated with RU28362 and corticosterone had substantially blunted stress-induced corticosterone and ACTH production, respectively. Furthermore, treatment with RU28362 significantly blunted stress-induced CRH hnRNA expression in the PVN. By contrast, neither RU28362 nor corticosterone treatment had an effect on stress-induced neuronal activation as measured by c-fos mRNA and its protein product in the PVN. This dissociation between c-fos and CRH gene expression suggests that glucocorticoid suppression of HPA activity within this time-frame is not a result of decreased excitatory neural input to the PVN, but instead depends on some direct effect of RU28362 on cells intrinsic to the HPA axis.
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PMID:Acute glucocorticoid pretreatment suppresses stress-induced hypothalamic-pituitary-adrenal axis hormone secretion and expression of corticotropin-releasing hormone hnRNA but does not affect c-fos mRNA or fos protein expression in the paraventricular nucleus of the hypothalamus. 1462 38

The hormonal response to stress is enhanced by oestrogen but inhibited by androgens. To determine underlying changes in activity of neuropeptide neurones in the paraventricular nucleus of the hypothalamus (PVN), we examined the effect of oestrogen and androgen treatment on restraint-induced c-fos mRNA, corticotropin-releasing hormone (CRH) heteronuclear RNA, and arginine vasopressin hnRNA expression in the PVN. Male rats were gonadectomized and injected with oestradiol benzoate (EB) or dihydrotestosterone propionate (DHTP; s.c., daily for 4 days). Rats were stressed by restraint for 10 min or 30 min before killing. Other rats were stressed for 30 min and then returned to their home cage for 20 min before killing. Corticosterone and adrenocorticotropic hormone responses to restraint stress were significantly greater in EB-treated rats and lower in DHTP-treated rats at the 30-min timepoint compared to controls. c-fos mRNA increases following stress were augmented by EB but inhibited by DHTP. CRH hnRNA expression increased significantly in the PVN in response to restraint stress, and this increase was augmented by EB treatment, but decreased by DHTP treatment. Vasopressin hnRNA expression was also increased in response to stress, and this increase was attenuated by DHTP. These findings indicate that gonadal hormones influence the reactivity of the hypothalamic-pituitary adrenal axis to stress.
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PMID:Androgen inhibits, while oestrogen enhances, restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus. 1504 58

Neuronal pathways involved in stress responses to extreme somatosensory stimuli were investigated by immunostaining, viral tract tracing, and experimental brain surgery in rats. Acute audiogenic stress, which elicits an immediate marked elevation in plasma ACTH and corticosterone concentrations, was used as a model. Loud noise (105 dB, 30 min) elicited c-fos activation within neurons in all of the components of the auditory system and stress-sensitive brain nuclei, including corticotropin-releasing hormone-synthesizing parvicellular neurons in the hypothalamic paraventricular nucleus (PVN). c-Fos activation was also seen in the medial paralemniscal nucleus in the pons (MPL) and in the subparafascicular nucleus (SPF) in the midbrain. After injection of neurotropic virus (pseudorabies, Bartha strain) into the PVN, neurons in the MPL and the parvicellular portion of the SPF were retrogradely infected. It has been shown by immunostaining that MPL and SPF neurons express a newly discovered neuropeptide, tuberoinfundibular peptide of 39 residues (TIP39). TIP39 is present in a fine neuronal network in the PVN. Audiogenic stress-elicited c-fos activation in TIP39-containing neurons of the MPL and SPF. TIP39 immunoreactivity disappeared from the PVN after transection of MPL and SPF projections to the nucleus. These observations suggest that TIP39-containing MPL and SPF neurons may participate in mediating audiogenic stress responses.
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PMID:Localization and chemical characterization of the audiogenic stress pathway. 1524 Mar 48

The c-fos knockout mice (c-fos KO) and corticotropin-releasing hormone knockout mice (CRH KO) can serve as interesting models for studying mechanisms involved in response of the organism to stress, focused mainly on the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenal system (SAS). The present study focused on the investigation of changes in gene expression of catecholamine biosynthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) in adrenal medulla of c-fos KO and CRH KO mice stressed by immobilization. Levels of TH, DBH, and PNMT mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR). Single immobilization for 2 h significantly increased adrenomedullary TH, DBH, and PNMT mRNA levels in both c-fos KO and wild-type (WT) mice compared to unstressed controls. In CRH KO mice, PNMT gene expression was not increased to the same extent after single, but especially after repeated immobilization as in WT mice, in contrast to TH and DBH mRNA levels. Thus, our data indicate that CRH deficiency can influence the PNMT mRNA level in adrenal medulla during stress, confirming the idea that the HPA axis plays the crucial role in PNMT gene regulation in mice. On the other hand, c-Fos protein probably does not play a crucial role in TH, DBH, and PNMT gene expression in adrenal medulla under stress conditions.
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PMID:Catecholamine synthesizing enzymes and their modulation by immobilization stress in knockout mice. 1524 Apr 2

Predators to rodents and their associated odors are increasingly chosen to study the neural mechanisms of stress and anxiety. Specifically, predatory odors are believed to elicit responses based on the perceived threat (psychological or processive), rather than to any direct systemic effects (pain, blood loss, infection, etc.) of the stimulus, which are mediated by distinct neural pathways. The hypothesis that a chemical component from fox feces, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), elicits stress responses by specific activation of processive neural pathways was tested. Different amounts of TMT (range: 0-600 micromol) or the control odor butyric acid (0-1200 micromol) were presented to male Sprague-Dawley rats for 30 min. Immediately after odor presentation, rats were sacrificed, blood levels of adrenocorticotropic hormone (ACTH) and corticosterone were measured, and brains were rapidly harvested to measure regional brain c-fos mRNA induction by in situ hybridization. Presentation of TMT (> or =75 micromol), but not butyric acid (up to 1200 micromol), significantly increased ACTH and corticosterone release. TMT presentation, especially with amounts (> or =75 micromol) producing endocrine activation, induced c-fos mRNA in several brain areas, including the olfactory bulb, lateral septal nucleus, septohypothalamic nucleus, anteromedial and oval nuclei of the bed nucleus of the stria terminalis, the central nucleus of the amygdala, the anteroventral, anterodorsal, and medial preoptic nuclei, the anterior, dorsomedial, lateral, supramammillary, dorsal premammillary and paraventricular hypothalamic nuclei, the external lateral parabrachial nucleus, the locus coeruleus, and the nucleus of the solitary tract. Interestingly, these brain regions represent a mix of regional c-fos mRNA induction pattern not reported previously with any other single stressor. These results suggest that TMT elicits stress responses through a relatively unique and complex mix of brain regions associated with both processive and systemic neural pathways, unlike those seen in response to cat odors.
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PMID:The pattern of brain c-fos mRNA induced by a component of fox odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), in rats, suggests both systemic and processive stress characteristics. 1546 54

Transplantation of adrenal medullary tissue for terminal cancer pain has been tested clinically, but this approach is not practical for routine use because of the shortage of organ donors and lack of tissue homogeneity. As a first alternative step, we have generated immortalized chromaffin cells over-expressing opioid peptides, namely met-enkephalin. Rat chromaffin cells have been genetically modified with vectors containing expression cassettes with either synthetic met-enkephalin or pro-enkephalin gene coding regions, fused with the nerve growth factor signal peptide for secretion. After stable transfection and differentiation in vitro, met-enkephalin and pro-enkephalin cells had higher met-enkephalin immunoreactivity and secreted met-enkephalin levels, compared to control cells containing the expression vector only. In the formalin hindpaw-injection model, 15 days after subarachnoid transplant of cells, grafts of met-enkephalin and pro-enkephalin cells significantly reduced the number of formalin-evoked c-fos immunoreactive spinal neurons in the spinal cord, compared to grafts of vector-alone chromaffin cells. The use of such expandable cell lines, for chronic spinal delivery of opiates, could offer an attractive and safe alternative strategy based on ex vivo gene therapy for the control of opioid-sensitive chronic pain.
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PMID:Grafts of immortalized chromaffin cells bio-engineered to improve met-enkephalin release also reduce formalin-evoked c-fos expression in rat spinal cord. 1548 7

We have previously reported that inescapable tail shock (IS) produces persistent changes in hypothalamic-pituitary-adrenal (HPA) axis function. These changes are manifest as an elevation in basal corticosterone (CORT) levels, a sensitization of adrenocorticotropin hormone (ACTH) and CORT responses to subsequent challenge, and a failure of dexamethasone to suppress both the ACTH and CORT responses to a subsequent challenge. The experiments presented here examine IS-induced alterations in the responsiveness of the HPA axis, particularly at the level of the anterior pituitary. The data presented show that adrenalectomy does not abolish the IS-induced sensitization of the HPA axis, suggesting that the sensitization is not solely caused by a defect in glucocorticoid negative feedback. Analysis of gene expression in the anterior pituitary revealed that IS exposure persistently elevated basal levels of proopiomelanocortin (POMC; the precursor to ACTH) mRNA and sensitized the POMC hnRNA and c-fos mRNA response to a subsequent challenge. Analysis of gene expression in the parvocellular division of the paraventricular nucleus of the hypothalamus (pPVN) after IS exposure revealed that basal levels of corticotropin-releasing hormone (CRH) mature mRNA are elevated and the c-fos mRNA response to a subsequent challenge is enhanced. Finally, a blunted in vitro ACTH response to CRH challenge is observed after IS exposure. These data suggest that the ultimate source of the IS-induced sensitization is not the anterior pituitary and implicate an increased drive on the anterior pituitary from the pPVN.
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PMID:Stress-induced sensitization of the hypothalamic-pituitary adrenal axis is associated with alterations of hypothalamic and pituitary gene expression. 1562 3

This study was conducted to examine stress-induced effects on gene expression of specific markers for HPA axis and neuronal activity in fetuses and neonatal pigs. Brain, pituitary gland, and adrenal gland were obtained to determine the mRNA levels for corticotropin-releasing hormone (CRH), CRH receptor 1 (CRHR1), pro-opiomelanocortin (POMC), ACTH receptor (MC2R), c-jun and c-fos. The suitability of these molecular markers was determined in neonatal pigs which were maternally deprived for two hours. It was found that maternal deprivation caused significantly higher transcript levels of c-fos and CRH in brain accompanied by a down-regulation of CRHR1 mRNA and an up-regulation of c-jun in the pituitary gland. To determine the effect of elevated maternal cortisol levels on gene expression of these molecular markers in fetuses, pregnant sows were treated with 100 IU ACTH (Synacthen Depot) s.c. every two days between Day 49 and Day 75 of gestation (normal gestation length 114 days). Animals were killed 48 hours after the last ACTH administration and fetuses of each sow were isolated. The ACTH treatment of sows significantly increased mRNA expression of c-fos but not of CRH in the fetal brain, and significantly decreased MC2R mRNA expression in the adrenal gland. However, HPA axis seems not to be fully developed in Day 77-fetuses because fetal pituitary CRHR1 and POMC mRNA expression was low in most of the fetuses. Although the expression of endocrine regulatory factors was partially incomplete in fetuses at the beginning of the third-trimester, ACTH dependent activation of c-fos mRNA in brain indicates a stress-related increase of neuronal activity. Based on these results it is assumed that prenatal stress in pigs may also have effects on the activity of the HPA axis in the offspring.
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PMID:Stress-related gene expression in brain and adrenal gland of porcine fetuses and neonates. 1571 Feb 5

Predator odors have been shown to elicit stress responses in rats. The present studies assessed the use of domestic ferret odor as a processive stress model. Plasma corticosterone and adrenocorticotropin hormone levels were higher after 30 min of exposure to ferret odor (fur/skin) but not control odors, ferret feces, urine, or anal gland secretions. Behavioral differences were also found between ferret and the control odors as tested in a defensive withdrawal paradigm. In addition, c-fos messenger RNA expression in several brain areas previously associated with processive stress was significantly higher in ferret odor-exposed rat brains than in control odor-exposed brains. These results suggest that ferret odor produces a reliable unconditioned stress response and may be useful as a processive stress model.
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PMID:Ferret odor as a processive stress model in rats: neurochemical, behavioral, and endocrine evidence. 1572 32


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