Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurons in the cat and monkey cerebral cortex were stained immunocytochemically for glutamic acid decarboxylase (GluDCase; L-glutamate 1-carboxy-lyase, EC 4.1.1.15), somatostatin (SRIF), neuropeptide Y (NPY), and cholecystokinin octapeptide (CCK). In all areas of cortex examined (somatic sensory, motor, parietal and visual areas), neurons displaying immunoreactivity for each of these molecules were nonpyramidal cells. Co-localization of GluDCase immunoreactivity with peptide immunoreactivity in the same cells was demonstrated by (i) the antibody elution method, staining the same cells by immunofluorescence, first for a peptide and then for GluDCase; (ii) double staining of the same sections with sheep anti-GluDCase and rabbit anti-peptide antisera, the bound antibodies being localized by rhodamine-conjugated donkey anti-sheep and fluorescein-conjugated swine anti-rabbit secondary antisera. With both procedures, cell bodies immunoreactive for GluDCase and for each of the peptides were found in all areas of cortex examined. With double labeling on single sections, it was found that all CCK-, SRIF-, and NPY-immunoreactive cells in cat cortex and 90%-95% in monkey cortex are also GluDCase positive. Many more cells, however, are immunoreactive for GluDCase alone. GluDCase was co-localized with CCK, SRIF, or NPY not only in cell somata, but also in small punctate structures, which are likely to be axon terminals. From the data gained in previous electron microscopic studies, we postulate that neurons displaying GluDCase- and CCK-like immunoreactivity are a class separate from those displaying GluDCase- and SRIF-like immunoreactivity. NPY, however, is co-localized with SRIF immunoreactivity. These results imply that classes of cortical interneuron contain a conventional neurotransmitter (gamma-aminobutyric acid) and a neuromodulator (one of the peptides).
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PMID:Neuropeptide-containing neurons of the cerebral cortex are also GABAergic. 614 47

The possible role that the hypothalamic arcuate nucleus might play in mediating the increase in paraventricular nucleus corticotropin-releasing hormone mRNA levels following adrenalectomy was investigated in two series of experiments. In the first series in situ hybridization histochemistry was used to quantify levels of eight accurate nucleus neuropeptide and neurotransmitter mRNAs in neurons that potentially relay adrenal steroid feedback to the paraventricular nucleus. In the second series of experiments, arcuate neuropeptidergic projections to the hypothalamic paraventricular nucleus were characterized using retrograde tracing in combination with in situ hybridization histochemistry. Despite an increase in paraventricular nucleus corticotropin-releasing hormone (60%) and pituitary proopiomelanocortin mRNA levels (sixfold), arcuate mRNA levels for proopiomelanocortin, neuropeptide Y, somatostatin, galanin, dynorphin, tyrosine hydroxylase, glutamate decarboxylase, and the glucocorticoid receptor were unchanged 14 days following adrenalectomy. Neuropeptidergic characterization of arcuatoparaventricular projections was achieved by injection of the retrograde tracer fluorogold into the paraventricular nucleus; retrogradely labeled neurons were characterized with polyclonal antisera against fluorogold in combination with oligonucleotide probes directed against neuropeptide Y, proopiomelanocortin, or somatostatin. Out of these three arcuate neuropeptide Y mRNA was contained in 18% of the fluorogold-positive neurons in the arcuate, proopiomelanocortin mRNA was contained in 8%, and somatostatin mRNA was contained in 6%. Overall, the results from both experiments suggest that the arcuatoparaventricular neuropeptide Y, proopiomelanocortin, and somatostatin projections are not sensitive to a chronic (14 day) lack of adrenal steroids. These projections as well as the other arcuate neurotransmitter and neuropeptide systems appear not to contribute to the persistent elevations in paraventricular nucleus corticotropin-releasing hormone mRNA levels or pituitary proopiomelanocortin mRNA levels found in 14 day adrenalectomized rats.
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PMID:Arcuate nucleus neurons that project to the hypothalamic paraventricular nucleus: neuropeptidergic identity and consequences of adrenalectomy on mRNA levels in the rat. 759 46

Gangliogliomas, dysembryoplastic neuroepithelial tumors (DNT) and glioneuronal malformations are frequently encountered in patients with pharmacoresistant focal epilepsies. In order to characterize the neurochemical profile of these neoplastic and malformative glioneuronal lesions, we have examined the presence of the alpha 1 subunit of the GABAA receptor, the N-methyl-D-aspartate receptor subunit 1 (NR1), glutamate decarboxylase, tyrosine hydroxylase, somatostatin, parvalbumin, and calretinin in 60 gangliogliomas, 11 DNT, 10 tuberous sclerosis-like lesions and 17 non-tuberous sclerosis-like glioneuronal malformations. All DNT and tuberous sclerosis-like lesions, 59 gangliogliomas (98%), and 13 non-tuberous sclerosis-like hamartias (76%) were positive for at least one of the markers. Despite a great variation between and within the different entities, the neurochemical profile was generally reminiscent of normal neocortex: glutamate decarboxylase, GABAA receptor and NR1 which are common in neocortical neurons were present in the great majority of the lesions and often showed high labeling indices. There were three tuberous sclerosis-like lesions (30%) that contained both NR1 and glutamate decarboxylase immunoreactive giant cells in addition to well-differentiated ganglion cells. This supports the idea that at least some of these giant cells are of neuronal origin. The oligodendroglia-like cells of DNT and glioneuronal hamartias did not show immunoreactivity for any of the markers. The very high incidence of ganglioglial lesions in patients with chronic focal epilepsies and the presence of neurotransmitter-producing enzymes, neurotransmitter receptors, neuropeptides, and calcium-binding proteins in many of these lesions suggests that they may play an active role in the pathogenesis of epileptic seizures.
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PMID:Neurochemical profile of glioneuronal lesions from patients with pharmacoresistant focal epilepsies. 766 58

The distribution and extent of glutamate decarboxylase 65 (GAD65) mRNA-labeled neurons that coexpress pre-prosomatostatin mRNA were studied in the rat dentate gyrus of the dorsal and ventral hippocampal formation. The distribution of each group of neurons was determined initially by nonradioactive in situ hybridization experiments with digoxigenin-labeled riboprobes for GAD65 mRNA and pre-prosomatostatin mRNA. Double labeling experiments were then conducted with digoxigenin-labeled riboprobes for GAD65 mRNA and 35S-labeled riboprobes for pre-prosomatostatin mRNA. In the dorsal and ventral dentate gyrus, GAD65 mRNA-containing neurons were highly concentrated in the hilus and in the innermost part of the granule cell layer whereas only a few labeled neurons were scattered in the molecular layer. Pre-prosomatostatin mRNA-containing neurons were primarily located in the hilus and were virtually absent from the molecular and granule cell layers. The simultaneous detection of GAD65 and pre-prosomatostatin mRNAs in the same sections showed that the vast majority of pre-prosomatostatin mRNA-containing neurons in the hilus of the dentate gyrus were also labeled for GAD65 mRNA. In contrast many GAD65 mRNA-labeled neurons did not contain pre-prosomatostatin mRNA. These included all neurons in the molecular layer, neurons within the inner granule cell layer and neurons interspersed amongst double labeled neurons in the hilus. Quantitative analyses indicated that a very high percentage of hilar pre-prosomatostatin mRNA-containing neurons coexpressed GAD65 mRNA in the dorsal (96%) and ventral (92%) dentate gyrus. In contrast only a part of the total population of hilar GAD65 mRNA-containing neurons were also labeled for pre-prosomatostatin mRNA in the dorsal (43%) and ventral (53%) dentate gyrus. In the CA3c region, the percentages of neurons containing both mRNAs were similar to those observed in the hilus. The findings demonstrate that the vast majority of hilar somatostatin neurons, which have previously been shown to be extremely vulnerable to ischemia and seizure-induced damage, are GABA neurons. However, the total population of GAD65 mRNA-containing neurons in the hilus is substantially larger than the somatostatin-containing subgroup, and these findings reinforce the suggestion that GABA neurons are a major component of the diverse group of neurons in the hilus of the dentate gyrus.
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PMID:Somatostatin neurons are a subpopulation of GABA neurons in the rat dentate gyrus: evidence from colocalization of pre-prosomatostatin and glutamate decarboxylase messenger RNAs. 770 May 25

This study determined differences of fascia dentata (FD) peptide and inhibitory neuroanatomy between patients with epileptogenic hippocampal sclerosis (HS), those with extrahippocampal seizure pathologies, and autopsy comparisons. Surgically treated temporal lobe epilepsy patients were clinically classified into two pathogenic categories: (1) HS with focal mesial temporal neuroimaging and histories of initial precipitating injuries to the brain (n = 18) and (2) non-HS patients with extrahippocampal mass lesions or idiopathic seizures (i.e., without lesions or HS; mass lesion/idiopathic; n = 9). The hippocampal sections were studied for (1) granule cell, hilar, CA4, and CA3 neuron densities; (2) hilar densities and the percentage of neurons immunoreactive (IR) for neuropeptide Y (NPY), somatostatin (SS), and glutamate decarboxylase (GAD); (3) densities of GAD neurons in the lower granule cell and infragranular zone (basket-like cells); (4) the semiquantitative pattern of IR peptides/GAD FD molecular layer axon sprouting; (5) IR gray values (GV) of the FD molecular layers; and (6) the thickness of the supragranular molecular layer. Results showed the following. (1) Compared to autopsies, both HS and mass lesion/idiopathic patients showed less granule cell and CA3 neuron densities, but there were no statistical differences between the latter two pathogenic categories. (2) By contrast, compared to autopsies and mass lesion/idiopathic cases, HS patients showed less hilar and CA4 neuron densities, and there were no differences between autopsies and mass lesion/idiopathic. (3) Compared to autopsies, the NPY and SS hilar neuron densities in HS patients, but not mass lesion/idiopathic cases, were less. (4) Compared to autopsies, the hilar GAD neuron densities for HS and mass lesion/idiopathic patients were not less. (5) In HS patients the averaged percentages of hilar SS neurons were less than autopsies, and no other differences of IR hilar percentages were found. (6) The densities of GAD basket-like neurons and the thickness of the supragranular molecular layer were not different between any combination of pathogenic categories and autopsies. (7) By semiquantitative visual assessments, peptides/GAD axon sprouting into the FD was greater in HS compared to mass lesion/idiopathic or autopsies. (8) Compared to mass lesion/idiopathic cases, in HS NPY outer molecular layer GVs were lower, SS GVs were not different, and GAD inner molecular layer GVs were higher. (9) Analyses comparing the two pathogenic categories and neuron densities with peptides/GAD axon sprouting found six comparisons that correlated sprouting with hilar and CA4 neuron losses, and four comparisons showing greater sprouting in HS compared to mass lesion/idiopathic.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata. 775 60

A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in the entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the immediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family (NGFI-B) and the interferon family (PC4) are increased within 2 h after the lesion and return to normal levels at 6 h. The messenger RNAs encoding cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are elevated within one day and return to normal levels after six days. An intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate, 30 min before surgery, prevented either the induction of immediate early gene expression or the increase of neuropeptide and glutamate decarboxylase messenger RNA expression. This study demonstrates that a minimal cortical lesion induces extensive changes in gene expression and that the mechanism(s) leading to these changes involves the action of glutamate at the N-methyl-D-aspartate receptor. These modifications may be of importance in explaining diffuse changes not related to neuronal circuitry in several conditions.
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PMID:Homolateral cerebrocortical increase of immediate early gene and neurotransmitter messenger RNAs after minimal cortical lesion: blockade by N-methyl-D-aspartate antagonist. 791 80

The neuropeptide-inducing activity of neurotrophic factors was tested in cultured cerebral cortical neurons. Brain-derived neurotrophic factor (BDNF) specifically increased contents of the neuropeptides somatostatin (SOM) and neuropeptide Y (NPY), but its effect on contents of cholecystokinin octapeptide and GABA was much less significant. The maximal induction of NPY content (15-fold increase) was achieved by 20 ng/ml of BDNF. These changes were also reproduced at the mRNA level. In contrast, neurotrophin-3 was much less potent at increasing NPY and SOM contents, and nerve growth factor had no effect on them. The expression of mRNA for NPY and SOM was fully dependent on the presence of BDNF in culture but irrelevant to the survival-promoting activity of BDNF, which has been reported previously. Most of the NPY immunoreactivity induced by BDNF was colocalized with glutamate decarboxylase immunoreactivity in cultured cortical neurons. These results suggest that BDNF regulates the peptidergic expression of GABAergic neurons in the cerebral cortex.
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PMID:Regulation of neuropeptide expression in cultured cerebral cortical neurons by brain-derived neurotrophic factor. 809 84

The alpha 1 subunit of the gamma-aminobutyric acid (GABA)A receptor is highly expressed in a subgroup of neurons in the hippocampal formation. The distribution and chemical identities of these neurons in the dentate gyrus have been studied with double-labeling in situ hybridization and immunohistochemical methods. Double labeling for the alpha 1 subunit and glutamate decarboxylase 65 (GAD65) mRNAs indicated that virtually all neurons in the dentate gyrus that are heavily labeled for the alpha 1 subunit are GABA neurons. However, many GAD65 mRNA-labeled neurons in the hilus do not contain high levels of the alpha 1 subunit mRNA and protein. Studies were thus conducted to determine if the somatostatin neurons of the hilus were part of the alpha 1 subunit-labeled group. Double labeling for the alpha 1 subunit and pre-prosomatostatin mRNAs demonstrated virtually no co-localization of these mRNAs in hilar neurons. Thus, the strongly labeled alpha 1 mRNA-containing neurons and the somatostatin neurons constitute two distinct populations of hilar GABA neurons. Double labeling for the alpha 1 subunit polypeptide and its mRNA with immunohistochemical and in situ hybridization methods demonstrated directly that neurons of the dentate gyrus that express high levels of the alpha 1 subunit mRNA are the same neurons that show extensive labeling for the alpha 1 subunit along their somal and dendritic surfaces. The high levels of alpha 1 subunit expression in some populations of GABA neurons could be related to prominent disinhibitory functions of these neurons.
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PMID:Subpopulations of GABA neurons in the dentate gyrus express high levels of the alpha 1 subunit of the GABAA receptor. 884 23

Accumulating evidence indicates that somatostatin (SS) is a key substance for the circadian rhythm of rodents. In the present study, we investigated whether SS mRNA coexists with arginine-vasopressin (AVP) mRNA, vasoactive intestinal peptide/peptide histidine isoleucine amide (VIP/PHI) mRNA and glutamate decarboxylase (GAD) mRNA in neurons of the rat suprachiasmatic nucleus (SCN) by double labeling in situ hybridization technique. SS mRNA-positive neurons were scattered in the whole region of rostral SCN, in the intermediate region between dorsomedial and ventrolateral region at the middle level, and in the mid to lateral region at the caudal level. These neurons were located in the close vicinities of the dorsomedial AVP and ventrolateral VIP/PHI mRNA-positive cell clusters. They rarely coexpressed AVP mRNA or VIP/PHI mRNA, but mostly coexpressed GAD mRNA. Thus, SS-synthesizing neurons are GABAergic and form a distinct cell group different from AVP or VIP/PHI cell groups.
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PMID:Somatostatin neurons form a distinct peptidergic neuronal group in the rat suprachiasmatic nucleus: a double labeling in situ hybridization study. 888 10

Patterns of co-localization of serotonin with glutamate decarboxylase (the synthetic enzyme for GABA) or each one of eight neuropeptides (calcitonin gene-related peptide, dynorphin, enkephalin, galanin, neuropeptide Y, neurotensin, substance P and somatostatin) were investigated with dual-colour confocal laser scanning microscopy in the lumbar spinal cords of three adult rats. Four regions of the gray matter were studied (laminae I-II, V, IX and X). The extent of co-localization was estimated by direct assessment of merged pairs of optical sections and by automated image analysis. Co-localization of serotonin and glutamate decarboxylase was found only in a few axons of laminae I-II but was not detected in other laminae. Peptides were not co-localized with serotonin in the superficial dorsal horn but considerable co-localization was found in motor nuclei and sparse co-localization was found in laminae V and X. Galanin and substance P frequently co-existed with serotonin in lamina IX but some co-localization with dynorphin, somatostatin, [Met]enkephalin and neuropeptide Y was also detected. Galanin, substance P and dynorphin were also co-localized with serotonin in a few axons of the deep dorsal horn and in the gray matter around the central canal. Neurotensin and calcitonin gene-related compound did not co-exist with serotonin in any of the laminae investigated. This evidence suggests that different populations of serotoninergic axons project to different regions of the spinal gray matter. Those containing glutamate decarboxylase terminate in the superficial dorsal horn and are likely to be involved in antinociception, whereas those containing peptides terminate principally in motor nuclei and are likely to modulate motor activity.
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PMID:A confocal microscopic survey of serotoninergic axons in the lumbar spinal cord of the rat: co-localization with glutamate decarboxylase and neuropeptides. 893 Oct 11


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