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)

Changes in the cholinergic, serotonergic, noradrenergic, dopaminergic, GABAergic and somatostatinergic neurons were investigated to determine their roles in Alzheimer's disease (AD). Markers for these systems were analyzed in postmortem brain samples from 20 patients with AD and 14 controls. In the CSF study, markers for the cholinergic neurons (choline esterase, ChE) and for the somatostatinergic neurons (somatostatin-like immunoreactivity, SLI) were assayed for 93 and 75 probable AD patients and 29 and 19 controls, respectively. Activity of choline acetyltransferase (CAT) was decreased by 50-85% in four cortical areas and hippocampus in patients with AD, but not in other areas of the brain, indicating a profound deficit in the function of cholinergic projections ascending from the nucleus basalis to the cerebral cortex and hippocampus in AD. Muscarinic receptor binding was reduced by 18% in the frontal cortex but not in other areas of the brain in AD. Serotonin (5HT) concentrations were reduced (by 21-37%) in hippocampal cortex, hippocampus and striatum; and 5HT metabolite levels were lowered (by 39-54%) in three cortical areas, thalamus and putamen in AD patients. Concentrations of noradrenaline (NA) were reduced (18-36%) in frontal and temporal cortex and putamen. These data imply that serotonergic and noradrenergic projections are also affected in AD but less than the cholinergic neurons. Dopamine (DA) concentrations in AD patients were reduced by 18-27% in temporal and hippocampal cortex and hippocampus, while HVA, the metabolite of DA, was unaltered. Glutamic acid decarboxylase activity was not altered in AD. SLI was decreased (28-42%) in frontal, temporal and parietal cortex, but not in thalamus and putamen in patients with AD. Frontal tangle scores correlated most strongly with cortical CAT activity reduction and less so with decreases of 5HT, NA and DA, indicating a closer correlation with the cholinergic changes and severity of AD than with other neurotransmitter deficiencies. ChE activity and SLI were reduced by 20% and 35%, respectively, in CSF of the whole group of AD patients as compared to the controls. Comparison of CSF findings between four subgroups of dementia severity indicated that the SLI was already reduced in the group of mildest AD (-31%), while ChE activity was not. Although ChE activity in CSF declined in relation to dementia severity, however, the maximal reduction was only modest (-30%). On the other hand, SLI in CSF showed only a slight further reduction (up to -41%) as the dementia become more severe.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotransmitter changes in Alzheimer's disease: implications to diagnostics and therapy. 198 17

The distribution of vasopressin-, vasoactive intestinal polypeptide-, somatostatin-, avian pancreatic polypeptide-, 5-hydroxytryptamine- and glutamic acid decarboxylase-like immunoreactivity was analyzed in the suprachiasmatic nuclei of male and female golden hamsters. Vasopressin. Vasopressin-like immunoreactivity is localized within neurons, dendrites and axons throughout the rostrocaudal extent of the suprachiasmatic nuclei. Immunoreactive perikarya are restricted to the dorsomedial aspect of each nucleus and occur in highest numbers within the intermediate two-thirds of the rostrocaudal axis. Axons containing vasopressin-like immunoreactivity form a dense plexus in the dorsomedial suprachiasmatic nuclei and in a vertical column at the lateral aspect of each nucleus. Somatostatin. Somatostatin-like immunoreactivity is also contained in neurons in the dorsomedial aspect of the suprachiasmatic nuclei and in thin varicose axons distributed throughout the suprachiasmatic nuclei in a pattern similar to that of vasopressin-immunoreactive axons. Vasoactive intestinal polypeptide. Vasoactive intestinal polypeptide-immunoreactive neurons are concentrated in the ventrolateral portion of each nucleus and occur almost exclusively within the intermediate two-thirds of the rostrocaudal axis. An extremely dense plexus of varicose axons exhibiting vasoactive intestinal polypeptide-like immunoreactivity extends throughout the suprachiasmatic nuclei and passes out of the dorsal aspect of each nucleus into the periventricular and anterior hypothalamic areas. Avian pancreatic polypeptide. Avian pancreatic polypeptide-like immunoreactivity is restricted to axons which arborize within the ventrolateral aspect of each nucleus. These fibers extend throughout the rostrocaudal extent of each nucleus and partially overlap the terminal field of retinal afferents. Glutamic acid decarboxylase. A very dense plexus of axonal varicosities exhibiting glutamic acid decarboxylase-like immunoreactivity fills both the dorsomedial and ventrolateral portions of the suprachiasmatic nuclei throughout the rostrocaudal extent of each nucleus. Lightly stained immunoreactive perikarya also occur throughout the suprachiasmatic nuclei. 5-Hydroxytryptamine. 5-Hydroxytryptamine-like immunoreactivity is restricted to axons which form a plexus in the ventromedial portion of each nucleus that is most dense in the intermediate two-thirds of the rostrocaudal axis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The suprachiasmatic nucleus of the golden hamster: immunohistochemical analysis of cell and fiber distribution. 615 Nov 47

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

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

The rostral nucleus of the solitary tract (rNST) plays a pivotal role in taste processing. The rNST contains projection neurons and interneurons that differ in morphology and intrinsic membrane properties. Although characteristics of the projection neurons have been detailed, similar information is lacking on the interneurons. We determined the intrinsic properties of the rNST GABAergic interneurons using a transgenic mouse model that expresses enhanced green fluorescent protein under the control of a GAD67 promoter. Glutamic acid decarboxylase-green fluorescent protein (GAD67-GFP) neurons were distributed throughout the rNST but were concentrated in the ventral subdivision with minimal interaction with the terminal field of the afferent input. Furthermore, the density of the GAD67-GFP neurons decreased in more rostral areas of rNST. In whole cell recordings, GAD67-GFP neurons responded with either an initial burst (73%), tonic (18%), or irregular (9%) discharge pattern of action potentials (APs) in response to membrane depolarization. These three groups also differed in passive and AP characteristics. Initial burst neurons had small ovoid or fusiform cell bodies, whereas tonic firing neurons had large multipolar or fusiform cell bodies. Irregular firing neurons had larger spherical soma. Some of the initial burst and tonic firing neurons were also spontaneously active. The GAD67-GFP neurons could also be categorized in subgroups based on colocalization with somatostatin and parvalbumin immunolabeling. Initial burst neurons would transmit the early dynamic portion of the encoded sensory stimuli, whereas tonic firing neurons could respond to both dynamic and static components of the sensory input, suggesting different roles for GAD67-GFP neurons in taste processing.
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PMID:Properties of GABAergic neurons in the rostral solitary tract nucleus in mice. 2037 46