Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The axonal transport blocker colchicine has been extensively used in immunohistochemical studies to induce accumulation of neuroactive compounds, especially neuropeptides, in neuronal somata and thus improve their visualization. To assess whether colchicine might, in addition, influence the synthesis of such compounds, we have now used in situ hybridization to examine the levels of mRNAs encoding for several neuropeptides (galanin [GAL], cholecystokinin [CCK], somatostatin [SOM], neuropeptide Y [NPY]) and neurotransmitter-synthesizing enzymes (choline acetyltransferase [ChAT], tyrosine hydroxylase [TH], amino acid decarboxylase [AADC], and glutamic acid decarboxylase [GAD]) after intraventricular administration of the drug. The results show that colchicine differentially modifies the levels of several mRNA species in different brain areas. Thus GAL mRNA levels increase in virtually all regions examined, including the basal forebrain, hypothalamus, dorsal raphe nucleus, locus coeruleus, and nucleus tractus solitarii. In addition, after colchicine treatment, GAL mRNA appears to be induced in the ipsilateral hemisphere in regions such as the cortex, hippocampus, striatum, lateral septum, and some nuclei of the thalamus as well as within white matter, where it cannot be detected in control animals. Although GAL mRNA in the vast majority of cases is neuronal, some findings indicate a possible glial localization. In parallel, colchicine depletes ChAT mRNA and increases GAD mRNA in the basal forebrain and striatum and decreases AADC mRNA in the dorsal raphe nucleus and locus coeruleus. In the latter nucleus, NPY and TH mRNA levels are increased by colchicine. In contrast, TH mRNA and also CCK mRNA levels decrease in the substantia nigra. In the cortex, hippocampus, and thalamus ipsilateral to colchicine injection CCK mRNA levels are markedly decreased, whereas SOM mRNA is decreased and NPY mRNA increased in the hippocampus but unchanged in the cortex. The results are discussed with reference to the possible artifacts that the use of colchicine might induce in immunohistochemical mapping studies and in relation to possible neurotoxic actions of colchicine, in some cases perhaps related to impaired retrograde transport of growth factor(s).
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PMID:Differential effects of intracerebroventricular colchicine administration on the expression of mRNAs for neuropeptides and neurotransmitter enzymes, with special emphasis on galanin: an in situ hybridization study. 170 58

We have used light-microscopical immunohistochemistry to investigate developmental changes of several neurochemical indicators in retinas of perinatal killifish and goldfish. Immunoreactive proliferating cell nuclear antigen (ir-PCNA/cyclin, a marker for replicating cells) was present in nuclei of all neuroblasts in the early monolayer stage, but was lost progressively in central-to-peripheral and proximal-to-distal order as the layers and cells of the mature retina appeared. The loss of ir-PCNA was slightly prior to the appearance of ir-TH (tyrosine hydroxylase), GAD (glutamic acid decarboxylase) and GS (glutamine synthetase) at the 4th embryonic day (E4) in both fish. Since hatching was earlier in goldfish (E5) than in killifish (E7), neurochemical maturation was evident at 2-3 days before hatching in killifish but not until around hatching in goldfish. Two markers, ir-somatostatin and protein kinase C, were detected by the 1st postnatal day (H1) in goldfish, but not in perinatal or adult killifish retinas. Thus the course of development of killifish and goldfish retinas is similar, but not identical. The validity of ir-PCNA as a marker for proliferating cells is confirmed by the coincidence of its disappearance with the appearance of neurochemical markers for mature, postmitotic retinal cells.
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PMID:Emergence and development of immunoreactive cells in teleostean retinas during the perinatal period. 197 54

Although Rolling mouse Nagoya (RMN) has been considered to demonstrate cerebellar dysfunction, our previous metabolic and electrophysiological studies also revealed a dysfunction of the basal ganglia, with the presumable primary site of dysfunction being the striatum. In the present study, we investigated the neurochemical functions of the striatum. In RMN, both preproenkephalin mRNA and preprotachykinin mRNA increased significantly in the striatum, with unaltered GAD mRNA, [(3)H]spiperone binding, [(3)H]QNB binding and preprosomatostatin mRNA, thus indicating the dysfunction of striatal projection neurons. These findings support the hypothesis that the site of primary dysfunction in the basal ganglia is in the striatum of RMN.
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PMID:Increased preproenkephalin mRNA and preprotachykinin mRNA in the striatum of Rolling mouse Nagoya. 886 30

Insulin-dependent (type I) diabetic patients are known to have an exaggerated growth hormone (GH) response to GH-releasing hormone (GHRH), which is hypothesized to be due to a decrease in somatostatin tone. The aim of the study was to ascertain the influence of the presence and activity of the autoimmune process involving a key enzyme (glutamic acid decarboxylase [GAD]) in the synthetic pathway of a neurotransmitter regulating somatostatin secretion, ie, gamma-aminobutyric acid (GABA), on the GH response to GHRH alone or combined with an acetylcholinesterase inhibitor, pyridostigmine (PD), in patients with type I diabetes mellitus. Twenty non-obese type I diabetic patients and 17 normal subjects underwent an intravenous (IV) injection of 100 micrograms GHRH(1-29)NH2. Twelve of 20 diabetic subjects and all of the control subjects also underwent a second experimental procedure, administration of 120 mg oral PD 60 minutes before IV injection of 100 micrograms GHRH. Diabetic subjects with serum GAD antibody (GADA) levels more than 3 U (n = 10) showed significantly higher serum GH levels after GHRH injection as compared both with diabetic patients with GADA less than 3 U (n = 10) and with normal controls, whether expressed as absolute or peak values. GH peaks after GHRH were significantly (rs = .46, P < .05) correlated with the level of GADA in the whole population of type I diabetic subjects studied. PD significantly enhanced the GH response to GHRH, in terms of both absolute and peak values, in patients without GADA (n = 6) and in normal subjects. On the contrary, PD failed to enhance the GH response to GHRH in diabetic patients with GADA (n = 6). Our findings suggest that autoimmunity may play a key role in determining the exaggerated GH response to GHRH in type I diabetes mellitus. The mechanism underlying this effect is hypothesized to be the production of antibodies to GAD, a key enzyme in the synthesis of GABA, and in turn a reduced GABAergic stimulatory tone on somatostatin production at the hypothalamic level.
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PMID:Glutamate decarboxylase autoimmunity and growth hormone secretion in type I diabetes mellitus. 910 40

The present study is the first to demonstrate conclusively and to analyze systematically synaptic contacts of all three types of catecholaminergic afferent fibers in different nuclei of the rat amygdala and to relate the catecholaminergic innervation to neurochemically identified target neurons. 4.1.1 Central Nucleus: The central nucleus is the amygdaloid nucleus receiving the most dense catecholaminergic innervation. In the medial central nucleus, dopaminergic, noradrenergic and adrenergic terminal plexus overlap, in the central lateral central nucleus mainly dopaminergic plexus are found. The lateral capsular central nucleus is generally scarcely innervated, but individual neurons of this subnucleus possess a dense dopaminergic innervation. Colocalization of neurotensin in dopaminergic afferents is rare, the majority of the dense neurotensin-ir terminal plexus consist of non-dopaminergic fibers. The catecholaminergic innervation of the medial central nucleus is directed preferentially at peripheral neuronal structures, and has thus presumably modulatory functions. Dopaminergic terminals form predominantly symmetric, noradrenergic and adrenergic terminals from preferentially asymmetric synapses. A characteristic feature of the dopaminergic innervation is the dense perisomatic innervation of selected neurons. Adrenergic and the majority of noradrenergic afferent fibers to the medial central nucleus originate from cell groups in the medulla oblongata and contain high levels of NPY. GAD mRNA-detection suggests that most target neurons of catecholaminergic afferent fibers are capable of synthesizing GABA in the medial central nucleus. In its dorsal part, GABA is possibly colocalized with somatostatin, and many neurons express the dopamine-1-receptor subtype mRNA. In the posteroventral medial central nucleus, on the other hand, enkephalin mRNA-r and dopamine-2-receptor subtype mRNA-reactive neurons show a similar distribution as the GAD mRNA-reactive ones. Contacts could be shown between dopaminergic, noradrenergic and adrenergic axons and NPY- and somatostatin-immunoreactive neurons which are supposedly among the brainstem projection neurons of the medial central nucleus. The dopaminergic innervation of the central lateral central nucleus resembles that of the neighboring striatum in many respects. The synaptic density is high. As in the medial subnucleus, distal neuronal elements are the preferential target structures, indicating a modulatory function possibly regulating the selectivity of the target neurons for stimuli transmitted by other afferent fibers. Besides, individual neurons possess a dense perisomatic, presumably non-selective dopaminergic innervation. The innervation does not appear to be targeted at one specific neurochemical type of neuron in the central lateral central nucleus, but rather contacts somatostatin- and neurotensin-immunoreactive neurons (which are possibly also GABAergic), in addition to GABA/enkephalin-synthesizing and other (e.g., CHAT-immunoreactive) neurons. Individual neurons of the central lateral central nucleus express the dopamine-2-receptor subtype mRNA. The dopaminergic fiber baskets of the lateral capsular central nucleus are found surrounding enkephalin mRNA-reactive neurons. Codistribution studies suggest that they express the dopamine-2-receptor subtype mRNA. 4.1.2 Basal Complex: The basal complex receives dopaminergic and noradrenergic innervation, the latter mainly originating in the locus coeruleus. Some of the dopaminergic afferents contain neurotensin, and in contrast to the central nucleus, all neurotensin-immunoreactive afferent fibers are dopaminergic. In the noradrenergic afferent fibers NPY is not detectable. These results and the innervation pattern displaying mostly peripheral neuronal target structures resemble dopaminergic and noradrenergic innervation patterns documented in cortical areas. (ABSTRACT TRUNCATED)
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PMID:The catecholaminergic innervation of the rat amygdala. 958 82

Patients with temporal lobe epilepsy display neuron loss in the hilus of the dentate gyrus. This has been proposed to be epileptogenic by a variety of different mechanisms. The present study examines the specificity and extent of neuron loss in the dentate gyrus of kainate-treated rats, a model of temporal lobe epilepsy. Kainate-treated rats lose an average of 52% of their GAD-negative hilar neurons (putative mossy cells) and 13% of their GAD-positive cells (GABAergic interneurons) in the dentate gyrus. Interneuron loss is remarkably specific; 83% of the missing GAD-positive neurons are somatostatin-immunoreactive. Of the total neuron loss in the hilus, 97% is attributed to two cell types-mossy cells and somatostatinergic interneurons. The retrograde tracer wheat germ agglutinin (WGA)-apoHRP-gold was used to identify neurons with appropriate axon projections for generating lateral inhibition. Previously, it was shown that lateral inhibition between regions separated by 1 mm persists in the dentate gyrus of kainate-treated rats with hilar neuron loss. Retrogradely labeled GABAergic interneurons are found consistently in sections extending 1 mm septotemporally from the tracer injection site in control and kainate-treated rats. Retrogradely labeled putative mossy cells are found up to 4 mm from the injection site, but kainate-treated rats have fewer than controls, and in several kainate-treated rats virtually all of these cells are missing. These findings support hypotheses of temporal lobe epileptogenesis that involve mossy cell and somatostatinergic neuron loss and suggest that lateral inhibition in the dentate gyrus does not require mossy cells but, instead, may be generated directly by GABAergic interneurons.
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PMID:Highly specific neuron loss preserves lateral inhibitory circuits in the dentate gyrus of kainate-induced epileptic rats. 1053 54

N-methyl-D-aspartate (NMDA) receptors are composed of subunits from two families: NR1 and NR2. We used a dual-label in situ hybridization technique to assess the levels of NR1 and NR2A-D messenger ribonucleic acid (mRNA) expressed in projection neurons and interneurons of the human striatum. The neuronal populations were identified with digoxigenin-tagged complementary RNA probes for preproenkephalin (ENK) and substance P (SP) targeted to striatal projection neurons, and somatostatin (SOM), glutamic acid decarboxylase 67 kD (GAD(67)), and choline acetyltransferase (ChAT) targeted to striatal interneurons. Intense NR1 signals were found over all striatal neurons. NR2A signals were high over GAD(67)-positive neurons and intermediate over SP-positive neurons. ENK-positive neurons displayed low NR2A signals, whereas ChAT- and SOM-positive neurons were unlabeled. NR2B signals were intense over all neuronal populations in striatum. Signals for NR2C and NR2D were weak. Only ChAT-positive neurons displayed moderate signals, whereas all other interneurons and projection neurons were unlabeled. Moderate amounts of NR2D signal were detected over SOM- and ChAT-positive neurons; GAD(67)- and SP-positive striatal neurons displayed low and ENK-positive neurons displayed no NR2D hybridization signal. These data suggest that all human striatal neurons have NMDA receptors, but different populations have different subunit compositions that may affect function as well as selective vulnerability.
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PMID:Expression of NMDA receptor subunit mRNAs in neurochemically identified projection and interneurons in the human striatum. 1074 12

We devised a real-time RT-PCR method for the quantification of preproinsulin 1 and 2, proglucagon, prosomatostatin, and GAD 65 and 67 mRNAs in the thymus, using specific primers and internal probes. Corresponding standard cRNA synthesis and normalization to 18S ribosomal RNA allowed direct quantification. Then, during the first month of life, the expression of each substance of interest was measured in the thymus of NOD mice (a spontaneous model of type 1 diabetes), C57BL/6, BALB/c and lymphocyte-deficient mice (NODscid, NODrag, BALB/cscid and C57BL/6rag). In all mouse thymuses, preproinsulin 1 and GAD 65 were undetectable, preproinsulin 2 and proglucagon showed low expression, whereas that of GAD 67 and somatostatin were high. In 7-day-old mice, GAD 67 and prosomatostatin thymic expressions were lower in NOD than in C57BL/6, and at the same age, the scid mutation but not the rag mutation induced higher expression of all investigated genes compared to control mice. In conclusion, our data allowed the quantification of the expression of pancreatic factors in the mouse thymus. Investigations are underway to quantify, at the cellular level, i.e., in thymic dendritic/macrophage cells, the RNA expression of potential autoantigens, such as preproinsulin 2 and GAD 67.
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PMID:Pancreatic hormone and glutamic acid decarboxylase expression in the mouse thymus: a real-time PCR study. 1135 61

We have previously demonstrated a 60-80% ischemic loss of somatostatinergic neurons in the dorsal dentate hilus of the rat. However, several studies have failed to demonstrate ischemic loss of GABAergic neurons in hilus, although one study reports that 96% of the somatostatinergic neurons in the dorsal hilus colocalize GABA. In order to understand this paradox, we have now estimated, using unbiased stereology, the total number of neurons immunohistochemically stained against glutamic acid decarboxylase-65 (GAD65) and GAD67 in the dorsal dentate hilus. Rats were divided into groups subjected to either sham operation (n=8) or 8 min of transient global ischemia during systemic hypotension (n=8) and allowed to survive for 7-9 days. Results from cell counts (mean +/- SD) in sham rats demonstrated that the dorsal hilus contains 9,189+/-3,957 GAD65 neurons and 6,991+/-2,784 GAD67 neurons. After ischemia, corresponding cell counts demonstrated 10,216+/-4,866 GAD65 neurons and 10,119+/-5,906 GAD67 neurons, and these results were not significantly different (P>0.05) from results in sham rats. Power analysis of the t-test informs that losses less than 80% are not significant and reflects the excessive variance in our material. For comparison, we estimated a total of 21% ischemic neuron death in the dorsal hilus on cresyl violet-stained sections from other corresponding sham (n=7) and ischemic rats (n=7). This explains why ischemic loss of hilar GABAergic neurons can only be detected by counts of the vulnerable subpopulation colocalizing somatostatin. Our investigation has demonstrated a surprisingly high variation between rats in a number of GAD-immunopositive neurons located in the dorsal dentate hilus, which is related to variations between the individual rats and neurons in their endogenous GAD expression.
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PMID:Stereological cell counts of GABAergic neurons in rat dentate hilus following transient cerebral ischemia. 1171 83

In the pilocarpine model of chronic limbic seizures, vulnerability of GABAergic interneurons to excitotoxic damage has been reported in the hippocampal CA1 region. However, little is known about the specific types of interneurons that degenerate in this region. In order to characterize these interneurons, we performed quantitative analyses of the different populations of GABAergic neurons labeled for their peptide or calcium-binding protein content. Our data demonstrate that the decrease in the number of GAD mRNA-containing neurons in the stratum oriens of CA1 in pilocarpine-treated rats involved two subpopulations of GABAergic interneurons: interneurons labeled for somatostatin only (O-LM and bistratified cells) and interneurons labeled for parvalbumin only (basket and axo-axonic cells). Stratum oriens interneurons labeled for somatostatin/calbindin or somatostatin/parvalbumin were preserved. The decrease in number of somatostatin- and parvalbumin-containing neurons was observed as early as 72 hours after the sustained seizures induced by pilocarpine injection. Many degenerating cell bodies in the stratum oriens and degenerating axon terminals in the stratum lacunosum-moleculare were observed at 1 and 2 weeks after injection. In addition, the synaptic coverage of the axon initial segment of CA1 pyramidal cells was significantly decreased in pilocarpine-treated animals. These results indicate that the loss of somatostatin-containing neurons corresponds preferentially to the degeneration of interneurons with an axon projecting to stratum lacunosum-moleculare (O-LM cells) and suggest that the death of these neurons is mainly responsible for the deficit of dendritic inhibition reported in this region. We demonstrate that the loss of parvalbumin-containing neurons corresponds to the death of axo-axonic cells, suggesting that perisomatic inhibition and mechanisms controlling action potential generation are also impaired in this model.
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PMID:Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures. 1268 7


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