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)

Biochemical indices of cortical nerve cells affected in Alzheimer's disease have been proposed (excitatory dicarboxylic amino acid, EDAA, sodium-dependent carrier; phosphate-activated glutaminase activity; serotonin type 2 recognition site; somatostatin-like immunoreactivity). These and the content of EDAAs and two related amino acids, and choline acetyltransferase (ChAT) activity have been measured in up to 13 areas of cerebral cortex and the cerebellar cortex from 16 patients with Alzheimer's disease and 17 controls. Reduction of the index of the serotonin recognition site, somatostatin content and another biochemical index of interneurones coincide and indicate a rather unexpected focal loss of such neurones from the parietal lobe. No unequivocal measure of the integrity of pyramidal neurones could be established as the content of no amino acid was reduced, the index of the EDAA carrier showed evidence of change in few brain regions and glutaminase activity was subject to unexplained variability. ChAT activity alone closely paralleled a previous report of the distribution of morphological degeneration. The results are discussed in relation to therapy and positron emission tomography.
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PMID:Topographical distribution of neurochemical changes in Alzheimer's disease. 289 11

Two populations of aspiny interneurons have been identified in the mammalian striatum, one cholinergic and the other using the neuropeptide somatostatin as a neurotransmitter. The times at which these 2 cell populations undergo their final mitosis were studied by injecting tritiated thymidine into timed pregnant rats and then processing the brains of the progeny as young adults for immunohistochemistry with monoclonal antibodies to choline acetyltransferase and somatostatin followed by autoradiography. Choline acetyltransferase-immunoreactive neurons became postmitotic in a caudal-to-rostral gradient; the occurrence of final mitosis was maximal on embryonic day (E) 12 at the most caudal level and on E15 at the most rostral. A more subtle lateral-to-medial gradient was also observed in the precommissural striatum. In contrast, no obvious gradients were seen with somatostatin-immunoreactive neurons; regardless of their location within the striatum, these neurons underwent their final mitosis on days E15-16, towards the end of cholinergic neurogenesis. These results indicate that although both cholinergic and somatostatin-containing cells represent interneuronal populations in the striatum, they display distinctly different spatiotemporal patterns of neurogenesis.
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PMID:Different times of origin of choline acetyltransferase- and somatostatin-immunoreactive neurons in the rat striatum. 290 16

Indirect immunofluorescence histochemistry was used to study the relation among GABAergic, catecholaminergic, cholinergic, and peptidergic neurons in the rat mediobasal hypothalamus. By employing a direct double-labelling procedure using sheep antiserum against glutamic acid decarboxylase (GAD), mouse monoclonal and rabbit antibodies to neurotensin (NT) and rabbit antisera to tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), galanin (GAL), growth hormone-releasing factor (GRF), or somatostatin (SOM), it was demonstrated that GAD-positive fibers and terminals in the external part of the median eminence co-contained immunoreactivity for TH, NT, GAL or GRF, but not for SOM. In the internal part of the median eminence-infundibular stalk, GAD-positive/NT-, GAL-, and GRF-negative and GAD-positive/TH-positive fiber plexa were shown. When a recently developed direct triple-labelling procedure with biotin-conjugated mouse secondary antibodies in conjunction with diethylaminocoumarin (DAMC)-conjugated avidin was employed, presence of GAD/GAL/NT- as well as GAD/GRF/NT-containing varicosities could be demonstrated close to hypophysial portal vessels. In colchicine-pretreated animals, GAD was shown to coexist with TH, NT, or GAL in cell bodies in both the dorsomedial and ventrolateral domains of the arcuate nucleus, but with GRF only in the ventrolateral division. ChAT-positive neurons in the ventrolateral region were also TH-positive. In the ventrolateral arcuate nucleus, triple-labelling followed by elution-restaining showed GAD/NT/GAL/TH-immunoreactivities in the same cells. Similarly, double-labelling with two following elution-restaining steps showed several NT/GAL/GRF/TH-containing cell bodies in this part of the arcuate nucleus. GAD-positive cells in the anterior hypothalamic periventricular area and fibers in the pituitary neurointermediate lobe were also TH-positive. The results demonstrate complex patterns of storage of chemical messengers in neurons of the arcuate nucleus-median eminence complex. Possible neuroendocrine interactions of these systems in the control of prolactin and growth hormone secretion are discussed.
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PMID:Peptide- and transmitter-containing neurons in the mediobasal hypothalamus and their relation to GABAergic systems: possible roles in control of prolactin and growth hormone secretion. 290 36

The distribution of neurons and fibres that contain substance P, cholecystokinin-8, vasoactive intestinal polypeptide, corticotropin-releasing factor, calcitonin-gene-related peptide, choline acetyltransferase, tyrosine hydroxylase, somatostatin, leucine-enkephalin, and neuropeptide Y was examined in the parabigeminal nucleus of the rat by immunohistochemistry. Many choline acetyltransferase-like immunoreactive or calcitonin-gene-related peptide-like immunoreactive neurons were observed in the dorsal, middle and ventral subdivisions of the parabigeminal nucleus. A few corticotropin-releasing factor-like immunoreactive neurons were also seen in these three subdivisions. The double-immunostaining demonstrated that some choline acetyltransferase-like immunoreactive neurons in the dorsal and ventral subdivisions contained calcitonin-gene-related peptide. Fibres containing cholecystokinin-8, substance P or vasoactive intestinal polypeptide were abundant in the parabigeminal nucleus. Fibres containing cholecystokinin-8 were concentrated in the dorsal and ventral subdivisions, and the lateral margin of the middle subdivision, whereas many fibres containing substance P or vasoactive intestinal polypeptide existed in the lateral half of each subdivision. Fibres containing calcitonin-gene-related peptide or corticotropin-releasing factor were mostly observed around the immunoreactive neurons. Tyrosine hydroxylase-like immunoreactive fibres were scattered in the parabigeminal nucleus.
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PMID:Localization of neuroactive substances in the rat parabigeminal nucleus: an immunohistochemical study. 290 92

A combination of immunocytochemical and enzyme histochemical methods have been used to study those neurons which survive lesions of the rat striatum, produced by low doses of the excitotoxin quinolinic acid. Nissl-stained sections revealed that following injection of this toxin many large neurons remained within areas of extensive cell loss. These large cells were found to express both the enzyme acetylcholinesterase and choline acetyltransferase-like immunoreactivity. The surviving cells did not contain the enzyme reduced nicotinamide adenine dinucleotide phosphate or the peptides, somatostatin and neuropeptide Y. This pattern of selective cell sparing was also found following lesions induced by low doses of the toxins ibotenic acid and kainic acid. The survival of large neurons indicates that the excitotoxin-lesioned rat striatum shares common features with the pattern of cell loss found in the caudate-putamen in Huntington's disease. The major difference between these two examples of striatal nerve cell degeneration is, however, the selective preservation of somatostatin/neuropeptide Y/nicotinamide adenine dinucleotide phosphate-diaphorase-containing neurons found in Huntington's disease but not observed following quinolinic acid lesions.
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PMID:Sparing of cholinergic neurons following quinolinic acid lesions of the rat striatum. 297 92

Alzheimer's disease is a progressive degenerative disease of the nervous system characterized neuropathologically by the presence of senile plaques and neurofibrillary tangles in amygdala, hippocampus and neocortex. Dysfunction and death of basal forebrain cholinergic neurones projecting to forebrain targets are associated with marked decreases in cholinergic markers, including the activity of choline acetyltransferase (ChAT). Although cortical levels of somatostatin and somatostatin receptors are reduced in Alzheimer's, no consistent changes have been reported in other neuropeptide systems. We have now examined in control and Alzheimer's brain tissues pre- and postsynaptic markers of corticotropin-releasing factor (CRF), a hypothalamic peptide regulating pituitary-adrenocortical secretion which also seems to act as a neurotransmitter in the central nervous system (CNS). We have found that in Alzheimer's, the concentrations of CRF-like immunoreactivity (CRF-IR) are reduced and that there are reciprocal increases in CRF receptor binding in affected cortical areas. These changes are significantly correlated with decrements in ChAT activity. Our results strongly support a neurotransmitter role for CRF in brain and demonstrate, for the first time, a modulation of CNS CRF receptors associated with altered CRF content. These observations further suggest a possible role for CRF in the pathophysiology of the dementia. Future therapies directed at increasing CRF levels in brain may prove useful for treatment.
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PMID:Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease. 300 85

The concentration of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), was measured in the cerebral cortex obtained at diagnostic craniotomy from 10 patients with Alzheimer's disease of 3 yrs mean duration and 6 patients with other causes of dementia, and from 31 subjects undergoing other neurosurgical procedures (for which removal of apparently normal tissue was necessary). GABA content of 5 areas of the cerebral cortex and the cerebellar cortex was measured postmortem in the brains of 23 Alzheimer and 19 control subjects and 5 patients with other causes of dementia. Fourteen of these specimens, including 7 from patients with Alzheimer's disease of 8 yrs mean duration, were obtained within 3 h of death. These were processed in a similar manner to the neurosurgical specimens and are regarded also as fresh tissue samples. The remaining 33 specimens are regarded as conventional postmortem samples as the mean interval of death to autopsy was 21 h. GABA concentration in conventional autopsy specimens from Alzheimer subjects was not reduced as compared with controls in either cingulate or cerebellar cortex. In the inferior parietal cortex, agonal status confounded this comparison. The concentration was reduced in superior parietal, frontal and temporal cortex but there is a possibility that agonal state also confounded these comparisons. There was no deficit in GABA concentration in fresh cortical tissue from Alzheimer patients except for the temporal lobe from autopsy specimens. The content of somatostatin-like immunoreactivity was, like GABA, found to be comparable to control in some groups of Alzheimer specimens. It is argued that the deficits in autopsy samples and lack of change in surgical specimens is likely to be due to the duration of illness at the time of sampling. Losses of choline acetyltransferase activity were observed in all groups of Alzheimer specimens in all areas of brain studied. The data are consistent with other results which suggest that cholinergic under-activity is most closely related to the clinical course of Alzheimer's disease.
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PMID:Gamma-aminobutyric acid concentration in brain tissue at two stages of Alzheimer's disease. 340 83

Post-mortem pathological and biochemical studies are reported on six patients with progressive dementia. The characteristic pathological finding was neurofilament-containing cytoplasmic inclusions in cortical and subcortical neurons. The clinical and pathological findings were consistent with so-called diffuse Lewy body disease. The patients had variable changes of the Alzheimer type, with five of six patients displaying "plaques only" Alzheimer's changes. Biochemical studies showed profound decreases in neocortical choline acetyltransferase (ChAT) activities that correlated with marked neuronal loss in the basal nucleus of Meynert. ChAT activities were normal in the hippocampus in three patients who also had no significant Alzheimer type hippocampal changes. All patients had decreased cortical somatostatin-like immunoreactivity. Our observations suggest that dementia in diffuse Lewy body disease bears biochemical similarities to Alzheimer's disease, in that biochemical markers for both intrinsic cortical neurons and ascending cholinergic neurons are affected.
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PMID:Diffuse Lewy body disease. Neuropathological and biochemical studies of six patients. 343 18

We have previously used organotypic cultures to study mechanisms regulating phenotypic expression of neurotransmitter characters in the brain. Our previous work indicated that nerve growth factor (NGF) specifically increased the activity of choline acetyltransferase (CAT) in striatal cholinergic interneurons. In the present study we examined the effect of NGF on neurons of fetal rat basal forebrain-medial septal area (BF-MS) maintained in organotypic culture. Treatment with 200 biological units/ml of NGF resulted in a 3- to 6-fold increase in the specific activity of CAT. This effect was specifically blocked by anti-NGF antiserum, whereas treatment with antiserum alone did not alter the cholinergic enzyme. NGF also elicited a marked increase in CAT staining intensity, using a monoclonal antibody directed against the enzyme. Further, the number of CAT-positive neurons appeared to increase in the NGF-treated cultures. Exposure to NGF also increased the activity of another cholinergic marker, the catabolic enzyme, acetylcholinesterase. The effect of NGF appeared to be highly selective, since substance P and somatostatin levels were unchanged by NGF treatment.
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PMID:Nerve growth factor selectively increases cholinergic markers but not neuropeptides in rat basal forebrain in culture. 360 70

To investigate changes in the somatostatinergic neurons of patients with Alzheimer's disease (AD), we determined the somatostatin-like immunoreactivity (SLI) in post-mortem brain tissue of histopathologically confirmed AD patients and in CSF of probable AD patients (according to DSM III). The CSF values were then correlated with psychological test scores. In 6 AD patients the SLI values were decreased 42% (P less than 0.005) in the frontal cortex, 28% (P less than 0.05) in the temporal cortex and 42% (P less than 0.01) in the parietal cortex but not in the thalamus and putamen compared to 11 control patients. In some brain areas there were statistical correlations between SLI values and cholinergic markers, choline acetyltransferase and acetylcholine esterase activities, suggesting a relationship between these two neurotransmitter systems. In the CSF among 75 AD patients SLI was 35% lower (P less than 0.001) than in controls. Severely demented power (P less than 0.001) than in controls. Severely demented patients showed lower SLI values than moderately demented individuals, but this difference was not significant. There was a weak but statistically significant correlation between SLI values in CSF and neuropsychological test scores. This study further confirms the involvement of somatostatinergic neurons in AD and suggests that this involvement may be related to the progression of dementia symptoms.
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PMID:Decreased somatostatin-like immunoreactivity in cerebral cortex and cerebrospinal fluid in Alzheimer's disease. 382 77


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