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 level of expression of mRNAs encoding somatostatin and two isoforms of glutamic acid decarboxylase (Mr 65,000, GAD65 and 67,000, GAD67) was examined by quantitative in situ hybridization histochemistry in the striatum of adult rats after local injections of quinolinic acid. After a 2-week survival period, Nissl strains showed a profound loss of neurons in the injected striata. With a dose of 120 nmol quinolinic acid, the lesioned area was completely devoid of somatostatin mRNA-positive neurons but contained cells expressing nicotinamide adenine dinucleotide-diaphorase activity (a marker of somatostatinergic interneurons in striatum). After 60 nmol of quinolinic acid, the number of neurons expressing somatostatin mRNA in the lesioned area was similar to controls but the level of labeling per neuron was increased. In the lesioned area, labeling for GAD65 mRNA was abolished and labeling for GAD67 mRNA markedly reduced. However, scattered neurons expressing GAD67 mRNA could still be detected. The majority of surviving GABA-ergic neurons expressed immunoreactivity to parvalbumin, a marker for striatal GABA-ergic interneurons. The results show that quinolinic acid induces dose-dependent alterations in the expression of striatal somatostatin mRNA and reveal a relative sparing of GABA-ergic interneurons in the quinolinic acid-lesioned rat striatum.
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PMID:Effects of quinolinic acid on messenger RNAs encoding somatostatin and glutamic acid decarboxylases in the striatum of adult rats. 134 22

Coexistence of NADPH-diaphorase (ND) activity and somatostatin (SRIF) immunoreactivity was studied in the paraventricular nucleus (PVN) of the rat hypothalamus by successive incubations of the same sections. ND was found in all PVN subdivisions, mainly in the magnocellular ones. SRIF was practically restricted to the parvicellular periventricular subdivision. Contrary to other brain regions where a wide SRIF-ND coexistence has been observed, the periventricular parvicellular subdivision was the only place of the PVN where some neurons colocalize both markers. The combination of the immunocytochemical and the histochemical labelings allows a further permanent and easy-to-perform parcellation of periventricular PVN neurons.
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PMID:Partial coexistence of NADPH-diaphorase and somatostatin in the rat hypothalamic paraventricular nucleus. 136 53

Previous studies have shown that nerve cells containing NADPH-diaphorase (NADPH-d) are relatively resistant to various damaging processes. NADPH-d has been found to be colocalized with somatostatin (SOM) and neuropeptide Y (NPY) in neuronal populations of several forebrain regions. We have investigated the anatomical distribution, morphology and cell sizes of NADPH-d neurons in amygdala and temporal cortex in Alzheimer's disease (AD) compared to controls of different age. NADPH-d cells and fibers were present in layers II-VI of the cortex and in the white matter below the cortical mantle. In the amygdaloid complex, NADPH-d cells and processes were observed in almost all subnuclei. In the amygdala of aged controls, only insignificant atrophic alterations of NADPH-d neurons and fibers were seen. In AD, a moderate, but significant shift towards an increased number of medium-to small-sized neurons was measured in amygdala and cortex, indicating cell shrinkage during the course of the disease. However, there were no differences when comparing NADPH-d staining in amygdaloid subregions in AD cases that contained numerous neuritic plaques (i.e., accessory basal nucleus) with areas that were relatively free of lesions (i.e., lateral nucleus). Analysis of cell size of SOM- and NPY-immunoreactive cells revealed only slight atrophic changes during aging. In AD, however, a significant atrophy of somatostatin neurons in temporal cortex was found, whereas no further cell shrinkage was noted for NPY as compared to aged controls. Colocalization tests demonstrated a large overlap between NPY, SOM and NADPH-d in the amygdala, whereas a subpopulation of cortical SOM neurons, predominantly localized in upper layers, showed a lack of NADPH-d. Our findings of a relative stability of a selective subclass of neurons during aging and AD support the hypothesis that cellular pathology may affect only specific neuronal populations while others might be spared.
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PMID:NADPH-diaphorase-positive cell populations in the human amygdala and temporal cortex: neuroanatomy, peptidergic characteristics and aspects of aging and Alzheimer's disease. 137 87

The intrastriatal infusion of relatively low doses of quinolinic acid (Quin, 4-10 nmol/h) for 1 or 2 weeks induced time-dependent degeneration of neuronal cells. We examined the effects of these infusions on discrete cellular populations. The distribution of somatostatin (SOM)-positive neurons labelled by immunocytochemistry or by NADPH-diaphorase histochemistry and of cholinergic cells stained by acetylcholinesterase was quantified in the peripheral portion of the lesioned area. SOM-positive cells did not appear selectively spared by Quin infusion. The proportion of SOM- and NADPH-diaphorase-positive neurons killed by exposure to Quin was similar to or higher than the percentage of total neurons degenerated (from 30 to 85%). A selective sparing of cholinergic cells was observed in all conditions examined; perfusion of 6 nmol/h for a week induced 65% of cell death while not more than 30% of cholinergic neurons were killed. Thus, the neurochemical similarity between the degenerative effects of intrastriatal Quin and Huntington's disease (HD) did not appear confirmed by the chronic perfusion of low doses of Quin for SOM-positive neurons, whereas an analogy between Quin's effects and HD was suggested by the pattern of AChE staining.
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PMID:Chronic infusion of quinolinic acid in rat striatum: effects on discrete neuronal populations. 138 77

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
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PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

Striatal atrophy in Huntington's disease (HD) is characterized by selective preservation of a subclass of neurons colocalizing NADPH-diaphorase (NADPH-d), somatostatin (SS), and neuropeptide Y (NPY), which have been reported to show three- to fivefold increases in SS-like immunoreactivity (SSLI) and NPY content. Since HD brain is capable of producing excessive quantities of the excitotoxin quinolinic acid (Quin), an N-methyl-D-aspartate (NMDA) receptor agonist, and since experimental Quin lesions show neuronal loss with sparing of NADPH-d/SS/NPY neurons, it has been suggested that Quin may be important in the pathogenesis of HD. In the present study we determined whether Quin stimulates SS gene function in cultured cortical cells known to be rich in NADPH-d/SS/NPY neurons. Cultures of dispersed fetal rat cortical cells were exposed to Quin (1 and 10 mM) with or without (-)-2-amino-5-phosphonovaleric acid (APV; 0.5 mM), an NMDA receptor antagonist, NMDA (0.2 and 0.5 mM), and glutamate (Glu; 0.5 mM). Medium and cellular SSLI was determined by radioimmunoassay and SS mRNA by Northern analysis with a cRNA probe. Quin induced significant (p less than 0.01) 1.6- and 2.5-4 fold increases in SSLI and SS mRNA accumulation, respectively, which were abolished by APV. Release of SSLI into the culture medium was stimulated two- to fivefold by Quin over a 2- to 20-h period. The increase in SS mRNA produced by Quin was time and dose dependent. A similar dose-dependent increase in SS mRNA comparable with that observed with Quin was induced by NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quinolinic acid stimulates somatostatin gene expression in cultured rat cortical neurons. 167 45

Transversal sections through the basal forebrain of 11 adult male rats were immunostained for glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT), somatostatin (SOM) and parvalbumin (PARV). Immunohistochemistry of ChAT, PARV, and SOM was combined with histochemistry of NADPH-diaphorase (NADPH-d) to obtain information on the colocalization of various neuroactive substances and this enzyme and to facilitate the recognition of morphological details of double-stained neurons. The distribution patterns of GAD- and PARV-immunoreactive cells were only in part congruent in basal forebrain nuclei in the rat. In the medial septal nucleus (MS) and the vertical limb of the diagonal band (vDB) PARV-immunopositive neurons were homogeneously scattered inside the nucleus, whereas the GAD-immunoreactive cells were much more numerous in the lateral part of this nuclear complex. In the horizontal limb of the diagonal band (hDB) and the nucleus preopticus magnocellularis (NPM), where GAD-immunoreactive cells occurred in high number, only very few cells contained PARV-immunoreaction product. In the substantia innominata-nucleus basalis Meynert complex (SI-NB) and in the ventral pallidum (VP) the neuropil was heavily stained with the GAD-immunoreaction product. The number of GAD-positive cells appeared low in the SI-NB, but much higher in the VP. In this nucleus GAD- and PARV-immunoreactive cells seem to be identical. PARV-positive neurons are very sparse in the SI-NB. Double-staining of PARV-immunoreactivity and NADPH-d was not registered. These nuclei were the only ones in which some cells with SOM-like immunoreactivity were observed. Among ChAT-positive neurons those double-stained with NADPH-d occurred in moderate number, but with obvious regional differences. In MS-vDB and the marginal zone of hDB the two neuron groups were intermingled, but only in the innermost part of the hDB ChAT-single-immunostained cells form aggregates, which were also typical of the zone in the SI-NB that surrounds and infiltrates the globus pallidus (GP). Double-labelled cells were more frequent in the lateral aspect of the NPM and SI-NB. Cells single-stained for NADPH-d were frequent in the MS-vDB along the border toward the lateral septal nuclei, but low in number in the NPM, VP and SI-NB. The functional aspects of the occurrence of GAD-immunoreactive cell aggregates in the lateral preoptic area (LP) and the lateral hypothalamic area (LH) were discussed with special regards to extrinsic GABAergic input in the dorsal SI-NB.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Morphology of neurons in the rat basal forebrain nuclei: comparison between NADPH-diaphorase histochemistry and immunohistochemistry of glutamic acid decarboxylase, choline acetyltransferase, somatostatin and parvalbumin. 168 12

L-Homocysteic acid (L-HCA) is a sulfated amino acid which is present in mammalian striatum and is a putative excitatory striatal neurotransmitter. In the present study we examined the histologic and neurochemical effects of L-HCA induced striatal lesions to determine how closely changes resemble those of Huntington's disease (HD). Increasing doses of L-HCA injected into the anterior striatum resulted in dose-dependent reductions in both substance P-like immunoreactivity (SP-LI) and gamma-aminobutyric acid (GABA) while there was a relative sparing of both somatostatin-like immunoreactivity (SS-LI) and neuropeptide Y-like immunoreactivity (NPY-LI). Immunocytochemical studies showed a relative sparing of NADPH-diaphorase neurons (which colocalize with SS and NPY) within regions in which there was a significant depletion of enkephalin stained neurons. The lesions were blocked by pretreatment with MK-801, a systemically effective non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors or coinjection of equimolar concentrations of 2-amino-5-phosphonovalerate (APV). These findings are similar to those produced with the NMDA agonist quinolinic acid, and suggest that other endogenous NMDA agonists, such as L-HCA, could be potential excitotoxins in HD.
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PMID:Homocysteic acid lesions in rat striatum spare somatostatin-neuropeptide Y (NADPH-diaphorase) neurons. 168 75

This study identifies the neuronal types of the rhesus monkey lateral entorhinal cortex (LEC) and discusses the importance of these data in the context of the connectional patterns of the LEC and the possible role of these cells in neurodegenerative diseases. These neuronal types were characterized with the aid of Golgi impregnation techniques. These characterizations were based upon their spine densities, dendritic arrays, and, where possible, axonal arborizations. The cells could be segregated into only spinous and sparsely spinous types. The most numerous spinous types were pyramidal neurons. Other spinous types included multipolar, vertical bipolar and bitufted, and vertical tripolar neurons. The sparsely spinous neuronal types consisted of multipolar, horizontal bipolar and bitufted, and neurogliaform cells. These cells were further classified with the aid of histochemical stains and immunocytochemical markers. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry stained multipolar, bipolar, and bitufted neurons. Stain for cytochrome oxidase (CO) was found in pyramidal and nonpyramidal cell types. Immunocytochemical techniques revealed several nonpyramidal neurons that contain somatostatin (Som) or substance P (SP). This study complements previous analyses of the neuronal components described in the LEC and adds further information about the distribution of selected neurochemicals within this cortex.
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PMID:Neurons of the lateral entorhinal cortex of the rhesus monkey: a Golgi, histochemical, and immunocytochemical characterization. 169 46

We previously found a relative sparing of somatostatin and neuropeptide Y neurons 1 week after producing striatal lesions with NMDA receptor agonists. These results are similar to postmortem findings in Huntington's disease (HD), though in this illness there are two- to threefold increases in striatal somatostatin and neuropeptide Y concentrations, which may be due to striatal atrophy. In the present study, we examined the effects of striatal excitotoxin lesions at 6 months and 1 yr, because these lesions exhibit striatal shrinkage and atrophy similar to that occurring in HD striatum. At 6 months and 1 yr, lesions with the NMDA receptor agonist quinolinic acid (QA) resulted in significant increases (up to twofold) in concentrations of somatostatin and neuropeptide Y immunoreactivity, while concentrations of GABA, substance P immunoreactivity, and ChAT activity were significantly reduced. In contrast, somatostatin and neuropeptide Y concentrations did not increase 6 months after kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) lesions. At both 6 months and 1 yr, QA lesions showed striking sparing of NADPH-diaphorase neurons as compared with both AMPA and KA lesions, neither of which showed preferential sparing of these neurons. Long-term QA lesions also resulted in significant increases in concentrations of both 5-HT and 5-hydroxyindoleacetic acid (HIAA), similar to findings in HD. Chronic QA lesions therefore closely resemble the neurochemical features of HD, because they result in increases in somatostatin and neuropeptide Y and in 5-HT and HIAA. These findings strengthen the possibility that an NMDA receptor-mediated excitotoxic process could play a role in the pathogenesis of HD.
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PMID:Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. 171 Jun 57


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