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)

The neuroanatomical distribution of nitric oxide synthase-immunoreactive neurons was investigated in post mortem hypothalami of 10 patients suffering from schizophrenia, eight patients with depression and 13 matched control cases. Neuronal nitric oxide synthase containing nerve cells were detected in several hypothalamic nuclei including the medial preoptic region, the ventromedial, infundibular and suprachiasmatic nuclei and the lateral hypothalamus. The vast majority of hypothalamic nitric oxide synthase-immunoreactive neurons was found to be located in the paraventricular nucleus. Both magno and parvocellular paraventricular neurons contained the enzyme. A small subset of immunoreactive parvocellular paraventricular neurons co-expresses corticotropin-releasing hormone. The supraoptic nucleus did not contain nitric oxide synthase-immunoreactive neurons. Cell counts of paraventricular nitric oxide synthase-positive neurons in controls, schizophrenics and depressed patients revealed a statistically significant reduction of cell density in the right paraventricular nucleus of depressed patients and schizophrenics as compared to controls. The total amount of nitric oxide synthase-immunoreactive paraventricular neurons was smaller in depressive and schizophrenic patients than in normal cases. The putative pathophysiologic significance of the reduced expression of paraventricular nitric oxide synthase in depressive patients might be related to the supposed regulatory function of nitric oxide in the release of corticotropin-releasing hormone and arginine-vasopressin and/or oxytocin, which have been reported to be over-expressed in the so-called endogenous psychoses, especially in depression.
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PMID:Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. 948 70

We investigated dose-dependent effects of alpha-melanocyte-stimulating hormone (alpha-MSH) on habituation in the Texas toad, Bufo speciosus. Additionally, we determined changes in plasma and brain levels of alpha-MSH following peripheral administration of the peptide or following exposure to an ether stressor. The ability of alpha-MSH to facilitate acquisition of habituation was dose dependent. Plasma alpha-MSH concentrations were elevated within 5 min of dorsal lymph sac injection and remained elevated up to 600% over controls after 30 min. Administration of 50 microgram alpha-MSH had no effect on plasma corticosterone levels. Radiolabeled alpha-MSH was detected in cerebrospinal fluid microdialysates within minutes of peripheral injection. Concentrations of alpha-MSH in the telencephalon and preoptic area were significantly lowered after ether exposure, whereas levels in the optic tectum, thalamus/hypothalamus, brainstem, and plasma were unchanged. We conclude that alpha-MSH administered peripherally facilitates habituation in a dose-dependent fashion. Our results confirm that the effects of alpha-MSH are independent of corticosterone secretion. The peptide is cleared rapidly into the bloodstream and enters the cerebrospinal fluid after dorsal lymph sac injection. Neuronal alpha-MSH may help toads gather information about their environment when exposed to certain stressors.
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PMID:alpha-melanocyte-stimulating hormone and habituation of prey-catching behavior in the Texas toad, Bufo speciosus. 1043 87

In addition to regulating the neuroendocrine stress response, corticotropin-releasing hormone (CRH) has been implicated in both normal and pathological behavioral and cognitive responses to stress. CRH-expressing cells and their target neurons possessing CRH receptors (CRF1 and CRF2) are distributed throughout the limbic system, but little is known about the regulation of limbic CRH receptor function and expression, including regulation by the peptide itself. Because CRH is released from limbic neuronal terminals during stress, this regulation might play a crucial role in the mechanisms by which stress contributes to human neuropsychiatric conditions such as depression or posttraumatic stress disorder. Therefore, these studies tested the hypothesis that CRH binding to CRF1 influenced the levels and mRNA expression of this receptor in stress-associated limbic regions of immature rat. Binding capacities and mRNA levels of both CRF1 and CRF2 were determined at several time points after central CRH administration. CRH downregulated CRF1 binding in frontal cortex significantly by 4 h. This transient reduction (no longer evident at 8 h) was associated with rapid increase of CRF1 mRNA expression, persisting for >8 h. Enhanced CRF1 expression-with a different time course-occurred also in hippocampal CA3, but not in CA1 or amygdala, CRF2 binding and mRNA levels were not altered by CRH administration. To address the mechanisms by which CRH regulated CRF1, the specific contributions of ligand-receptor interactions and of the CRH-induced neuronal stimulation were examined. Neuronal excitation without occupation of CRF1 induced by kainic acid, resulted in no change of CRF1 binding capacity, and in modest induction of CRF1 mRNA expression. Furthermore, blocking the neuroexcitant effects of CRH (using pentobarbital) abolished the alterations in CRF1 binding and expression. These results indicate that CRF1 regulation involves both occupancy of this receptor by its ligand, as well as "downstream" cellular activation and suggest that stress-induced perturbation of CRH-CRF1 signaling may contribute to abnormal neuronal communication after some stressful situations.
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PMID:Corticotropin-releasing hormone (CRH) downregulates the function of its receptor (CRF1) and induces CRF1 expression in hippocampal and cortical regions of the immature rat brain. 1209 84

Neuronal plasticity during the critical postnatal period of development seems to promote a change in the function of the hypothalamic regulatory system of body weight. Rats raised in small litters (SL) of only three pups per mother compared to ten or twelve in control litters (CL) gain significantly more weight than normal rats till weaning and are overweight also in later life. These rats are known to express hyperleptinemia, hyperglycemia and hyperinsulinemia. The review summarizes the results of action of leptin and insulin as well as of several feeding-relevant neuropeptides on neuronal activity of hypothalamic regulatory centres in overweight SL rats compared to controls. The study was performed on brain slices perfused with solution containing 10 mM glucose. Whereas a normally inhibitory action of leptin and insulin on medial arcuate neurons (ArcM) is reduced in SL rats and partly replaced by activation, the normally activating effect of these hormones on ventromedial (VMH) neurons is altered to predominant inhibition. Inhibition of ArcM neurons may decrease the release of the orexigenic neuropeptide Y (NPY) and agouti gene-related protein (AGRP). Thus, the negative feedback by leptin and insulin on food intake is replaced by diminished response and partly positive feedback processes in SL rats. The action of NPY and AGRP as well as of the orexigenic melanin-concentrating hormone on paraventricular (PVH) and VMH neurons is also shaped from activation or bimodal effects to predominant inhibition. Such inhibition of PVH and VMH might lead to reduced energy expenditure in small litter rats. Also the anorexigenic melanocortin alpha-MSH seems to contribute into increased energy storage. These altered responses of hypothalamic neurons in overweight small litter rats might reflect a general mechanism of neurochemical plasticity and "malprogramming" of hypothalamic neuropeptidergic systems leading to a permanently altered regulatory function.
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PMID:Altered neuronal responses to feeding-relevant peptides as sign of developmental plasticity in the hypothalamic regulatory system of body weight. 1465 33

Topographical distribution of estrogen receptor-beta (ER-beta)-synthesizing oxytocin (OT) and vasopressin (VP) neurons was studied in the hypothalamic paraventricular and supraoptic nuclei (PVH; SO) of ovariectomized rats. In distinct subregions, 45-98% of OT neurons and 88-99% of VP neurons exhibited ER-beta immunoreactivity that was confined to cell nuclei. Neuronal populations differed markedly with respect to the intensity of the ER-beta signal. Magnocellular OT neurons in the PVH, SO, and accessory cell groups typically contained low levels of the ER-beta signal; in contrast, robust receptor labeling was displayed by OT cells in the ventral subdivision of medial parvicellular subnucleus and in the caudal PVH (dorsal subdivision of medial parvicellular subnucleus and lateral parvicellular subnucleus). Estrogen receptor-beta signal was generally more intense and present in higher proportions of magnocellular and parvicellular VP vs. OT neurons of similar topography. Immunocytochemical observations were confirmed via triple-label in situ hybridization, an approach combining use of digoxigenin-, fluorescein-, and 35S-labeled cRNA hybridization probes. Further, ER-beta mRNA was also detectable in corticotropin-releasing hormone neurons in the parvicellular PVH. Finally, double-label immunocytochemical analysis of human autopsy samples showed that subsets of OT and VP neurons also express ER-beta in the human. These neuroanatomical studies provide detailed information about the topographical distribution and cellular abundance of ER-beta within subsets of hypothalamic OT and VP neurons in the rat. The variable receptor content may indicate the differential responsiveness to estrogen in distinct OT and VP neuronal populations. In addition, a relevance of these findings to the human hypothalamus is suggested.
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PMID:Estrogen receptor-beta in oxytocin and vasopressin neurons of the rat and human hypothalamus: Immunocytochemical and in situ hybridization studies. 1511 94

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

Opioids have impact on stress responses and possess immune modulatory functions. We have previously shown that immune stress elevates the levels of preproenkephalin transcript in a variety of autonomic structures in the rat brain, including the paraventricular hypothalamic nucleus. By using in situ hybridization with an intronic probe recognizing the preproenkephalin heteronuclear RNA combined with retrograde tract tracing, we examined the efferent target of the enkephalinergic neurons in the paraventricular hypothalamic nucleus that display induced transcriptional activity during immune challenge. Rats were first given i.p. injections of the tracer substance Fluoro-Gold, which following this route of administration is taken up only by nerve terminals residing outside the blood-brain barrier, and were then given an i.v. injection of lipopolysaccharide. Neuronal cell bodies retrogradely labeled with Fluoro-Gold were detected by immunohistochemistry, and-using a dual-labeling approach-the same cells were then examined for their expression of preproenkephalin heteronuclear RNA. We found that over 90% of the neurons that expressed preproenkephalin heteronuclear RNA also contained Fluoro-Gold. In addition, approximately 40% of the neurons expressing preproenkephalin heteronuclear RNA co-expressed mRNA for corticotropin-releasing hormone, the main adrenocorticotropic hormone secretagogue. These data show that the paraventricular hypothalamic neurons that display induced preproenkephalin transcription following immune challenge are almost exclusively hypophysiotropic neurons, indicating a role for enkephalin in the hypothalamic control of hormone release during infectious and inflammatory conditions.
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PMID:Lipopolysaccharide induces preproenkephalin transcription in hypophysiotropic neurons of the rat paraventricular hypothalamic nucleus suggesting a neuroendocrine role for enkephalins during immune stress. 1694 13

Corticotropin releasing factor (CRF), localized in afferent inputs to the cerebellum, binds to two receptors defined as the Type 1 (CRF-R1) and the Type 2 (CRF-R2alpha). CRF-R1 has been localized to the cerebellum, as has a truncated isoform of CRF-R2alpha. Evidence for the presence of the full length isoform of CRF-R2alpha in the cerebellum is conflicting. We used RT-PCR, immunohistochemical, and physiologic techniques to resolve this conflict. RT-PCR data show low levels of CRF-R2alpha in the vermis and hemisphere of the cerebellum. These observations were confirmed by the Gene Expression Nervous System Atlas (GENSAT) database. A CRF-R2alpha antibody was used to determine the cellular distribution of the receptor in the cerebellum. The vast majority of the receptors are localized to Bergmann glial cells located throughout the cerebellum, as well as astrocytes in the granule cell layer. Neuronal labeling is present in sub-populations of Purkinje cells, Golgi cells, basket cells, and cerebellar nuclear neurons. Physiologic data show that urocortin II, which binds selectively to CRF-R2alpha, increases the firing rate of both Purkinje cells and nuclear neurons; this response can be blocked by the CRF-R2alpha-specific antagonist, antisauvagine-30. The present results confirm that CRF-R2alpha is present in the cerebellum and functions in circuits that modulate the firing rate of Purkinje cells and cerebellar nuclear neurons. A comparative analysis showed that the patterns of distribution of CRF-R1, CRF-R2alpha and CRF-R2alpha-tr are distinct. These data indicate that the CRF family of peptides modulates cerebellar output by binding to multiple CRF receptors.
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PMID:Evidence for the presence of the type 2 corticotropin releasing factor receptor in the rodent cerebellum. 1695 82

Neuronal networks originating in the hypothalamic arcuate nucleus play fundamental roles in the control of energy balance. Neuropeptide Y (NPY)-producing neurons in the arcuate nucleus stimulate food intake, whereas arcuate nucleus neurons that release the proopiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone (alpha-MSH) potently reduce food intake. Relatively little attention has been focused on classical neurotransmitters in regulation of food intake. Here, we have investigated the potential presence of acetylcholine (ACh) in NPY- and POMC-containing neuronal populations of the arcuate nucleus. Antisera to proteins required for cholinergic neurotransmission, including choline acetyltransferase (ChAT) and the vesicular acetylcholine transporter (VAChT), were employed in double-labeling immunohistochemical experiments. In colchicine-treated rats, ChAT- and VAChT-immunopositive cell bodies were located in the ventral aspect of the arcuate nucleus. ChAT and VAChT immunoreactivities were demonstrated in alpha-MSH- and cocaine- and amphetamine-regulated transcript (CART)-containing cell bodies of the arcuate nucleus, whereas cell bodies containing NPY or agouti-related peptide (AGRP) were distinct from VAChT-immunoreactive neuronal perikarya. VAChT immunoreactivity was also present in a large number of alpha-MSH-containing nerve fiber varicosities throughout the central nervous system. In the commissural part of the nucleus tractus solitarius, no alpha-MSH-containing cell bodies were found to have ChAT or VAChT immunoreactivity. The presence of markers for cholinergic neurotransmission in a subpopulation of hypothalamic POMC/CART neurons suggests co-release of ACh with peptides derived from the POMC precursor and CART. The results indicate a role for ACh in control of energy balance, mediating the effects of peripheral hormones such as leptin and insulin.
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PMID:Hypothalamic proopiomelanocortin (POMC) neurons have a cholinergic phenotype. 1715 99

The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) release from the pituitary, which subsequently causes cortisol release from the adrenal cortex. The CRH neurons co-express vasopressin (AVP) which potentiates the CRH effects. CRH neurons project not only to the median eminence but also into brain areas where they, e.g., regulate the adrenal innervation of the autonomic system and affect mood. The hypothalamo-neurohypophysial system is also involved in stress response. It releases AVP from the PVN and the supraoptic nucleus (SON) and oxytocin (OXT) from the PVN via the neurohypophysis into the bloodstream. The suprachiasmatic nucleus (SCN), the hypothalamic clock, is responsible for the rhythmic changes of the stress system. Both centrally released CRH and increased levels of cortisol contribute to the signs and symptoms of depression. Symptoms of depression can be induced in experimental animals by intracerebroventricular injection of CRH. Depression is also a frequent side effect of glucocorticoid treatment and of the symptoms of Cushing's syndrome. The AVP neurons in the hypothalamic PVN and SON are also activated in depression, which contributes to the increased release of ACTH from the pituitary. Increased levels of circulating AVP are also associated with the risk for suicide. The prevalence, incidence and morbidity risk for depression are higher in females than in males and fluctuations in sex hormone levels are considered to be involved in the etiology. About 40% of the activated CRH neurons in mood disorders co-express nuclear estrogen receptor (ER)-alpha in the PVN, while estrogen-responsive elements have been found in the CRH gene promoter region, and estrogens stimulate CRH production. An androgen-responsive element in the CRH gene promoter region initiates a suppressing effect on CRH expression. The decreased activity of the SCN is the basis for the disturbances of circadian and circannual fluctuations in mood, sleep and hormonal rhythms found in depression. Neuronal loss was also reported in the hippocampus of stressed or corticosteroid-treated rodents and primates. Because of the inhibitory control of the hippocampus on the HPA-axis, damage to this structure was expected to disinhibit the HPA-axis, and to cause a positive feedforward cascade of increasing glucocorticoid levels over time. This 'glucocorticoid cascade hypothesis' of stress and hippocampal damage was proposed to be causally involved in age-related accumulation of hippocampal damage in disorders like Alzheimer's disease and depression. However, in postmortem studies we could not find the presumed hippocampal damage of steroid overexposure in either depressed patients or in patients treated with synthetic steroids.
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PMID:The stress system in depression and neurodegeneration: focus on the human hypothalamus. 1752 88


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