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)

Senile dementia of the Alzheimer's type can be diagnosed with certainty only by examining neurofibrillary tangles and neuritic plaques under the microscope. Recently, it has been suggested that the condition is linked to specific neurotransmitter systems, with a decline of cortical acetylcholine, choline acetyltransferase, cholinergic neurones projecting to the cortex, cortical noradrenaline content, locus coeruleus neurones and cortical somatostatic content. Using immunocytochemical methods, we here report that somatostatin-immunoreactive processes are present in neuritic plaques in human Alzheimer's specimens. These data, as well as other reports of non-cholinergic changes, strongly imply that Alzheimer's disease cannot be linked exclusively to cortical cholinergic elements, as proposed previously. Rather, our data on plaque and somatostatin co-localization and distribution patterns suggest that Alzheimer's neuropathology may involve primarily the loss of selective cortical neurones that are targets of the implicated transmitter systems and that plaque formation may result from the degeneration of presynaptic and postsynaptic neurites of large projection neurones in layers III and V. Given the neurochemically heterogeneous input to these cells, it is not surprising that several neurotransmitter systems, one of which is somatostatin, are implicated in the pathology of Alzheimer's disease.
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PMID:Somatostatin immunoreactivity in neuritic plaques of Alzheimer's patients. 285 56

Immunocytochemistry (ICC) and a reverse hemolytic plaque assay for GH were used to investigate the temporal relationships between the initiation of hormone storage and release by developing somatotropes and the onset of responsiveness of these cells to stimulatory and inhibitory secretagogues. Anterior pituitaries obtained from rats on days 18-21 of fetal development (pups were generally delivered on fetal day 22, which is equivalent to day 0 of neonatal life) were monodispersed with trypsin, cultured for 24 h, and then subjected to reverse hemolytic plaque assay and/or ICC for GH. GH-containing cells (determined by ICC) were extremely rare (less than 1%) in cultures derived from day 18 fetuses, but accounted for 22.4%, 25.2%, and 24.5% of all cells in cultures from day 19-21 fetuses, respectively. The proportion of GH-releasing cells, as determined in a long term (120-min incubation with antibody) plaque assay, was less than 1%, 22.4%, and 22.9% for days 18, 20, and 21, respectively, but only 13.6% for day 19 cells. Thus, many pituitary cells from day 19 fetuses contained, but did not release, GH. While GH-releasing factor (1-44) (1 X 10(-7) M) had no effect on the percentage of GH plaque-forming cells in long term incubations, it enhanced (by approximately the same degree in day 19-21 groups) the percentage of cells that formed plaques and the size of the plaques in short term (45-min) incubations with antibody. Somatostatin (1 X 10(-7) M) exerted inhibitory effects on these variables when tested in long term incubations, and age of the donor rats did not influence pituitary responsiveness to this secretagogue. These results suggest that the capacities of fetal somatotropes to store GH and release it under basal and regulated conditions are attained, in large part, within an extremely narrow time frame between days 18 and 19 of fetal development.
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PMID:Functional maturation of somatotropes in fetal rat pituitaries: analysis by reverse hemolytic plaque assay. 285 84

Alzheimer's disease or senile dementia of the Alzheimer type (SDAT) is a progressive neurodegenerative disease that is characterized pathologically by two types of microscopic lesions in the neocortex: the neurofibrillary tangle and neuritic plaque. The concentration of neuritic plaques is correlated with significant reductions in the level of specific neurotransmitter and neuropeptide systems in autopsied brains of patients with SDAT, including decreased amounts of the tetradecapeptide, somatostatin. The clinical effects of reduced cortical somatostatin activity in patients with SDAT is unclear, nor is it known whether somatostatinergic neurons participate in either lesion. In the present study we employed light microscopic immunocytochemistry to determine whether somatostatin-containing neurons participate in the formation of neuritic plaques. Examination of selected cortical regions from autopsied brains revealed 20-50% of all neuritic plaques contained somatostatin-positive profiles indicating that processes of somatostatinergic neurons are associated with neuritic plaque formation.
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PMID:Somatostatin-like immunoreactivity within neuritic plaques. 286 52

Senile plaques participate in a cropping of the dendritic tree of enkephalinergic dentate granule cells and hl and subicular pyramidal cells. Somatostatin-containing pyramidal neurons are lost in Alzheimer's disease, whereas nonpyramidal somatostatin neurons are less affected. Fibers containing somatostatin penetrate immature, but not end-stage senile plaques. The senile plaque may precipitate much of the hippocampal denervation seen in Alzheimer's disease.
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PMID:Role of the senile plaque in neuropeptide deficits of Alzheimer's disease. 286 94

The evidence for deficiencies in neurotransmitters in Alzheimer's disease is reviewed. Major losses occur in the subcortical afferent projection systems based on acetylcholine, noradrenaline and serotonin. Within the cortex, somatostatin containing neurones and the large pyramidal cells, presumed to use glutamate/aspartate as transmitters, are the most severely damaged cells. The anatomical distribution of cell loss is explainable if the primary site of damage lies within the cortex; nerve cells are damaged by virtue of their presence within or their connections to this region. The senile plaque may represent the site of this damage and neurofibrillary tangle formation and accumulation may lead to cell death. In patients with Down's syndrome who live past 40 years, changes in transmitters apparently identical to those in Alzheimer's disease occur. The dementia of Parkinson's disease appears related to damage to cholinergic, noradrenergic and dopaminergic systems and may reflect a failure of these subcortical regions to sufficiently "activate" an otherwise undamaged cortex.
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PMID:Neurotransmitter deficits in Alzheimer's disease and in other dementing disorders. 287 73

The content of two neuropeptides, somatostatin (SRIF) and neuropeptide Y (NPY) has been determined in two cerebral cortical areas of Alzheimer's disease brain and in age-matched control brains. The content of SRIF-like immunoreactivity (SRIF-LI) was found to be decreased in Alzheimer temporal cortex (Brodmann area 21) compared to control temporal cortex. The decreased content of SRIF was significantly correlated with the observed number of neuritic plaques and neurofibrillary tangles. No difference was observed in NPY-LI between Alzheimer cerebral cortex and control cortex. Furthermore, no correlations were observed between NPY content and plaque count, neurofibrillary tangle estimate or SRIF content despite widespread reports of NPY/SRIF coexistence.
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PMID:Decreased somatostatin immunoreactivity but not neuropeptide Y immunoreactivity in cerebral cortex in senile dementia of Alzheimer type. 287 20

It is generally accepted that hypothalamic somatostatin and hepatic insulin-like growth factor I (IGF-I)/somatomedin-C act directly on the pituitary to inhibit GH release, but it is not known whether all somatotropes are responsive to these agents. In the present study, we used a reverse hemolytic plaque assay to compare the acute (8 h) effects of somatostatin and IGF-I on the release of GH from individual cells in 24-h cultures of male rat pituitaries. Treatment with these factors caused comparable dose-dependent decreases in both the rate of plaque formation and the percentage of cells which released GH. In 8-h incubations, maximal (10(-8) M) doses of IGF-I or somatostatin alone decreased the percentage of GH-releasing cells to approximately the same degree (from 34.4% in controls to 29.7% and 28.4%, respectively), yet the effects of these factors were additive when both agents were applied to the same cells (to 24.5%). When we analyzed the sizes of plaques (an index of the amount of hormone released per cell) which resulted from these treatments, we noted that somatostatin was a much greater suppressor (to 11% of control value) of GH release than IGF-I (60% of controls). Coincubation with 10(-8) M GH-releasing factor had no effect on the percentage of GH-releasing cells at 8 h but completely overrode the inhibitory effect of IGF-I on plaque size without affecting the somatostatin-induced decrease in this regard. Taken together, these data suggest that IGF-I and somatostatin act, at least in part, on separate subpopulations of rat somatotropes. Somatostatin is a much more effective inhibitor of total GH release than IGF-I and appears to affect most, if not all, somatotropes. In contrast, IGF-I acutely inhibits GH release (prevents plaque formation) from some somatotropes, but does not seem to affect the remaining GH cells.
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PMID:Existence of somatotrope subpopulations which are differentially responsive to insulin-like growth factor I and somatostatin. 288 99

The long-term effects of excitotoxic lesions in the nucleus basalis magnocellularis of the rat were found to mimic several neuropathological and chemical changes associated with Alzheimer's disease. Neuritic plaque-like structures, neurofibrillary changes, and neuronal atrophy or loss were observed in the frontoparietal cortex, hippocampus, amygdala, and entorhinal cortex 14 months after the lesions were made. Cholinergic markers in neocortex were reduced, while catecholamine and indoleamine metabolism was largely unaffected at this time. Bilateral lesions of the nucleus basalis magnocellularis increased somatostatin and neuropeptide Y in the cortex of the rat by at least 138 and 284 percent, respectively, suggesting a functional interaction between cholinergic and peptidergic neurons that may differ from that in Alzheimer's disease.
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PMID:Long-term neuropathological and neurochemical effects of nucleus basalis lesions in the rat. 289 Feb 10

Eighteen patients with psoriatic arthritis were treated for 48 hours with an infusion of somatostatin 250 micrograms/hr diluted in a 5% glucose solution. This therapy led to a reduction of joint pain and satisfactory clearing of cutaneous lesions immediately after treatment in eight patients, less marked results in four, and null in four. Two patients were dropped from the study because of negative side effects during administration of the drug. Fifteen days after treatment, the clearing of lesions and joint pain reduction were even more pronounced. The most encouraging results were obtained on erythrodermic and large plaque psoriasis and on the polyarticular involvement. We suggest that the use of this drug, whose side effects are discussed, should be limited to patients with polyarthritis showing severe cutaneous involvement.
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PMID:Somatostatin treatment of psoriatic arthritis. 289 65

Somatostatin and neuropeptide Y are two neuropeptides that are of particular interest in Alzheimer's disease because they are reported to be depleted in cerebral cortex. In the present study we examined somatostatin, neuropeptide Y, and nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase neurons in nine cortical regions in both normal and Alzheimer's disease brains. These three neurochemical markers show a high degree of co-localization (greater than 90%) in nonpyramidal neurons that are primarily distributed in cortical layers II-III, V-VI, and, most prominently, in infracortical white matter. The highest cell density was in temporal and parietal association cortex. The major morphological abnormality in Alzheimer's disease brains was a marked pruning and distortion of fiber plexuses with an apparent reduction in fiber density. In contrast, perikaryal density was preserved except for a reduction in parietal association cortex. Approximately 10 to 15% of senile plaques in the inferior temporal gyrus contained abnormal neurites. Additional abnormal collections of neurites without plaque cores were frequently found in layers II-III and V-VI. Neuropeptide Y and somatostatin were co-localized in abnormal neurites, suggesting an origin from local intrinsic neurons in which the two peptides are co-localized. Double immunofluorescence staining for both tau protein, a major antigenic component of paired helical filaments, and either somatostatin or neuropeptide Y showed that these neurons do not contain tau-immunoreactive neurofibrillary tangles. The morphological correlate of reduced somatostatin and neuropeptide Y content in Alzheimer's disease brain therefore appears to be a distortion and reduction in fiber plexuses. In addition, it is apparent that these neurons can develop widespread morphological abnormalities in the absence of neurofibrillary tangle formation.
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PMID:Cortical somatostatin, neuropeptide Y, and NADPH diaphorase neurons: normal anatomy and alterations in Alzheimer's disease. 289 22


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