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

The influence of neurotrophins on GABAergic properties of developing striatal neurons was investigated both in vivo and in vitro. Brain-derived neurotrophic factor (BDNF) specifically elevated cellular GABA content in striatal culture without altering neuronal survival. Neurotrophin-5 produced a similar effect on GABA, but nerve growth factor and neurotrophin-3 had no effect. An increase in GABA content in the striatum was also observed following BDNF injections into the cerebroventricle of neonatal rats. The increase of GABA levels in culture mainly resulted from an increase in holoenzyme activity of the GABA synthetic enzyme glutamic acid decarboxylase (GAD) and elevation of GABA uptake activity. In BDNF-treated striatal cultures, the newly differentiated neurons extended elaborate neurites and exhibited strong GAD immunoreactivity. These alterations were presumably caused by the upregulation of mRNA encoding GAD67 and the neuronal GABA transporter GAT-1. BDNF treatment also promoted other phenotypic differentiation of striatal neurons: BDNF increased the frequency of parvalbumin-immunoreactive neurons and calbindin-immunoreactive neurons and neuropeptide content for neuropeptide Y and somatostatin. These observations suggest that neurotrophins may contribute to phenotypic differentiation of GABAergic neurons in the developing striatum.
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PMID:Brain-derived neurotrophic factor promotes differentiation of striatal GABAergic neurons. 808 42

Glutamic acid decarboxylase (GAD) has been shown to exist as two isoforms with molecular weights of 65 kD (GAD65) and 67 kD (GAD67) in the central nervous system as well as in several non-neuronal tissues, including the pancreatic islets. Recently, this enzyme has been proposed as a key beta-cell autoantigen in insulin-dependent diabetes mellitus (IDDM). In the present study, we used double label light and confocal microscopy to examine the expression of the two GAD isoforms in islet cells of fetal, neonatal and adult porcine pancreas. We also aimed to identify the islet cell-type(s) which co-express GAD. In the adult pig, GAD65 was localized exclusively in most of the beta cells, whereas GAD67, in addition to being present in a majority of the beta cells, was also seen in a proportion of glucagon and somatostatin labelled cells. In the 90-day fetus and the 7-day neonate, while GAD65 was also observed in a majority of beta cells, a proportion of glucagon cells also co-expressed this isoform. The cellular expression of GAD67 in the fetal and neonatal stages was similar to that in the adult. Detailed confocal analysis of GAD65 immunoreactive cells showed a granular cytoplasmic staining, with labelled granules often concentrated in specific perinuclear regions, possibly the Golgi apparatus. In contrast, GAD67 positive cells showed more diffuse cytoplasmic staining. The predominant expression of both the isoforms in porcine beta cells suggests that islet cells from this species may act as a suitable cellular model for study of GAD autoreactivity during the early stages of IDDM.
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PMID:Glutamic acid decarboxylase 65 and 67 isoforms in fetal, neonatal and adult porcine islets: predominant beta cell co-localization by light and confocal microscopy. 884 50

NMDA receptors are composed of proteins from two families: NMDAR1, which are required for channel activity, and NMDAR2, which modulate properties of the channels. The mRNA encoding the NMDAR2D subunit has a highly restricted pattern of expression: in the forebrain, it is found in only a small subset of cortical, neostriatal and hippocampal neurons. We have used a quantitative double-label in situ hybridization method to examine the expression of NMDAR2D mRNA in neurochemically defined populations of neurons. In the neostriatum, NMDAR2D was expressed by the interneuron populations marked by preprosomatostatin (SOM), the 67-kDa form of glutamic acid decarboxylase (GAD67), parvalbumin (PARV), and choline acetyltransferase (ChAT) mRNAs but not by the projection neurons expressing beta-preprotachykinin (SP) or preproenkephalin (ENK) mRNAs. In the neocortex, NMDAR2D expression was observed in only a small number of neurons, but these included almost all of the SOM-, GAD67-, and PARV-expressing interneurons. In the hippocampus, NMDAR2D was not present in pyramidal or granule cells, but was abundant in SOM-, GAD67-, and PARV-positive interneurons. NMDAR2D expression appears to be a property shared by interneurons in several regions of the brain. The unique electrophysiological characteristics conveyed by this subunit, which include resistance to blockade by magnesium ion and long channel offset latencies, may be important for the integrative functions of these neurons. NMDAR2D-containing receptor complexes may prove to be important therapeutic targets in human disorders of movement. In addition, the presence of NMDAR2D subunits may contribute to the differential vulnerability of interneurons to excitotoxic injury.
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PMID:Expression of NMDAR2D glutamate receptor subunit mRNA in neurochemically identified interneurons in the rat neostriatum, neocortex and hippocampus. 891 84

Fetal dopaminergic neurons grafted into the dopamine-depleted striatum have previously been shown to normalize neurochemical and behavioural abnormalities. However, the extent of graft-induced recovery of striatal compartments, which differ in their ontogeny, neurochemical properties and function, is still not clear. The striosome and matrix compartments of the striatum provide a segregated projection to somatostatin-containing GABAergic neurons of the rostral part of the entopeduncular nucleus and somatostatin-negative GABAergic neurons of the caudal part of the entopeduncular nucleus, respectively. In the present study, preprosomatostatin and glutamate decarboxylase messenger RNA levels in the rostral and caudal parts of the entopeduncular nucleus were determined six and 18 months postgrafting in rats with complete recovery of rotational behaviour following apomorphine challenge, and in rats with unilateral 6-hydroxydopamine lesions or sham lesions and no grafts. Sections were processed for in situ hybridization using 35S-labelled cRNA probes for glutamate decarboxylase (67,000 mol. wt isoform; GAD67) and preprosomatostatin. Autoradiographs showed a marked increase in preprosomatostatin messenger RNA within the ipsilateral entopeduncular nucleus in 6-hydroxydopamine-lesioned rats, and a substantially lower increase six months postgrafting. At 18 months postgrafting, the preprosomatostatin messenger RNA levels were symmetrical within the entopeduncular nucleus. Unilateral depletion of striatal dopamine resulted in a moderate increase in GAD67 messenger RNA levels within the ipsilateral entopeduncular nucleus, along with a substantial decrease in GAD67 levels within the contralateral nucleus. By six months postgrafting, the GAD67 levels had decreased considerably within the ipsilateral entopeduncular nucleus, while the messenger RNA levels had returned to normal within the contralateral nucleus. Interestingly, at 18 months postgrafting, the GAD67 levels remained decreased within the ipsilateral entopeduncular nucleus and were significantly lower than the normal value. The results indicate that fetal nigral grafts placed within the dopamine-depleted striatum can restore the neurochemical alterations seen in striatal target areas such as the entopeduncular nucleus. This may form the neurochemical basis of graft-induced behavioural recovery, as the normalization of neurotransmitter messenger RNA levels in the entopeduncular nucleus reflects the restoration of overall activity in both direct and indirect striatal output pathways. The results also indicate that the graft-derived dopaminergic innervation restores the output of both striosome and matrix compartments of the striatum. The present results also showed a progressive recovery leading to over-compensation of neurotransmitter messenger RNA levels following grafting, perhaps indicating the importance of feedback regulation of grafted dopaminergic neurons by the host.
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PMID:Effects of graft-derived dopaminergic innervation on the target neurons of patch and matrix compartments of the striatum. 902 77

In the striatum, interneurons have not been as well characterized physiologically as the spiny projection cells. We found that the neostriatal interneurons can be divided at least into three classes by physiological, chemical and morphological criteria. The first was FS cells (fast-spiking cells) which fired very short-duration action potentials at constant spike frequency during depolarizing pulses, were immunoreactive for parvalbumin (calcium-binding protein), and had axons with very dense collateralization within or near their dendritic fields. Another class was identified as those which fired low-threshold spikes (LTS cells) from hyperpolarized potentials, were positive for somatostatin and nitric oxide synthase (NOS), and had the largest axonal fields. The other class of interneurons had longer-lasting afterhyperpolarizations (LA cells), were positive for choline acetyltransferase, and were mostly large aspiny cells. Glutamic acid decarboxylase (GAD67) or GABA immunoreactivity was detected at the somata or terminals of parvalbumin FS cells and somatostatin/NOS LTS cells, but not of cholinergic LA cells. Substance P, probably released from the collaterals of cells projecting to the substantia nigra, excited LA cells and LTS cells, but not FS cells. These results suggest that the striatum has at least one type of cholinergic and two types of GABAergic interneurons which are different in physiological, chemical and pharmacological characteristics.
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PMID:Cholinergic and GABAergic interneurons in the striatum. 920 28

Glutamic acid decarboxylase (GAD) is present in the central nervous system and in several nonneuronal tissues including the pancreatic islets. There are two isoforms with molecular weights of 65 kDa (GAD65) and 67 kDa (GAD67). The cellular specificity of the two molecular forms of GAD and their levels within the mammalian islets may be species-dependent, being coexpressed in both beta and in non-beta cells. We have examined the ovine pancreas, from the adult and fetal stages of late gestation, for the expression of GAD65 within the islet cells by double-label immunofluorescence light and confocal microscopy. In the adult tissue, GAD65 was colocalized in a majority of the beta cells (> 95%), with only a few glucagon and somatostatin cells (< 5%) showing immunolocalization. During the fetal stages GAD65 also showed a similar predominant beta-cell coexpression. The enzyme was also detected in a few fetal glucagon (< 5%) but not somatostatin cells. In the degenerating large fetal islets, GAD65 was also observed in the majority of the residual beta cells. These results demonstrate that in the ovine pancreas GAD65 is expressed during fetal development and is predominantly beta-cell-restricted. This pattern of expression is maintained during adult life. However, the physiological role of pancreatic GAD and/or its biosynthetic product, gamma-aminobutyric acid, in islet function in the sheep and in other ruminants remains unclear.
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PMID:Double-label immunofluorescence study of glutamic acid decarboxylase in the fetal and adult ovine pancreas by light and confocal microscopy: evidence for predominant beta-cell coexpression. 920 63

Subplate neurons, the first neurons of the cerebral cortex to differentiate and mature, are thought to be essential for the formation of connections between thalamus and cortex, such as the system of ocular dominance columns within layer 4 of visual cortex. To learn more about the requirement for subplate neurons in the formation of thalamocortical connections, we have sought to identify the neurotransmitters and peptides expressed by the specific class of subplate neurons that sends axonal projections into the overlying visual cortex. To label retrogradely subplate neurons, fluorescent latex microspheres were injected into primary visual cortex of postnatal day 28 ferrets, just prior to the onset of ocular dominance column formation. Subsequently, neurons were immunostained with antibodies against glutamate, glutamic acid decarboxylase (GAD-67), parvalbumin, neuropeptide Y (NPY), somatostatin (SRIF), or nitric oxide synthase (NOS). Retrograde labeling results indicate that the majority of subplate neurons projecting into the cortical plate reside in the upper half of the subplate. Combined immunostaining and microsphere labeling reveal that about half of cortically projecting subplate neurons are glutamatergic; most microsphere-labeled subplate neurons do not stain for GAD-67, parvalbumin, NPY, SRIF, or NOS. These observations suggest that subplate neurons can provide a significant glutamatergic synaptic input to the cortical plate, including the neurons of layer 4. If so, excitation from the axons of subplate neurons may be required in addition to that from lateral geniculate nucleus neurons for the activity-dependent synaptic interactions that lead to the formation of ocular dominance columns during development.
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PMID:Major glutamatergic projection from subplate into visual cortex during development. 970 30

We have analyzed the effects of a small cortical infarct which is known to induce dramatic changes in gene expression in the entire cerebral cortex, on the gene expression in the striatum, a target structure of cortical neurons. Striatal glutamic acid decarboxylase (GAD67) and enkephalin expressions were increased in the striatum ipsilateral to the lesion. Conversely, neuropeptide Y- and somatostatin-like immunoreactivity were decreased in the ipsilateral striatum and this decrease was only related to a decrease in the labeling of processes with no changes in the number of labeled neurons. A minimal cortical lesion may therefore induce changes in gene expression in a subcortical structure through hyperactivity of glutamatergic synaptic inputs. One should therefore remember these extensive and long-lasting effects when surgical manipulations are performed on rat brain for stereotaxic surgery and placement of electrodes or probes.
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PMID:Changes in striatal neuropeptides and GAD67 expression following a minimal cortical lesion. 1054 11

Huntington's disease is a devastating progressive neurodegenerative illness characterized by massive neuronal loss in the striatum. It is caused by the presence of an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. We have examined the expression of neurotransmitters and other antigens present in striatal neurons with immunohistochemistry, and the level of expression of mRNAs encoding enkephalin, substance P, and glutamic acid decarboxylases with quantitative in situ hybridization histochemistry, in the striatum of two mouse models of Huntington's disease: transgenic animals expressing exon 1 of the human huntingtin gene with 144 CAG repeats and "knock-in" mice containing a chimeric mouse/human exon 1 with 71 or 94 CAG repeats inserted by homologous targeting. Although the transgenic (but not the knock-in) mice were previously shown to display prominent huntingtin- and ubiquitin-containing nuclear inclusions in striatal neurons, in situ nick translation followed by emulsion autoradiography did not reveal any DNA damage in striatum or cortex in these mice. Immunolabeling for calbindin D 28K, enkephalin, substance P, glutamic acid decarboxylases (M(r) 65,000 or 67,000, GAD65 and GAD67), somatostatin, choline acetyltransferase, parvalbumin, and glial fibrillary acidic protein were remarkably similar in transgenic, knock-in, and wild-type mice. Both transgenic and knock-in mice, however, showed a marked decrease in the level of expression of enkephalin mRNA in striatal neurons without significant decreases in mRNAs encoding substance P, GAD65, or GAD67. The data indicate that decreased expression of enkephalin mRNA may be an early sign of neuronal dysfunction due to the Huntington's disease mutation.
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PMID:Decrease in striatal enkephalin mRNA in mouse models of Huntington's disease. 1073 39


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