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)

To clarify the functional role of the brain somatostatinergic system in cognitive processes, changes in the performance in passive avoidance and water maze tasks and in brain somatostatin contents were comparatively investigated in young Fischer rats subjected to brain cholinergic and somatostatinergic depletion, and in aged Fischer rats. Lesioning of the nucleus basalis magnocellularis and administration of cysteamine (200 mg/kg, s.c.), a depletor of somatostatin, resulted in significant deficits in passive avoidance, but complete transection of the fimbria-fornix hardly affected the performance in the task. When cognitive performance was assessed in the Morris water maze, lesions of the nucleus basalis magnocellularis and the fimbria-fornix, and administration of cysteamine, significantly impaired the acquisition of navigatory spatial memories of rats. On the other hand, aged rats (24-27 months) showed severe impairments of memory acquisition in both tasks. Neurochemistry measurements showed that lesions of the nucleus basalis magnocellularis produced a selective reduction both in the cortical cholinergic marker choline acetyltransferase and in striatal somatostatin level, whereas lesioning of the fimbria-fornix caused a marked loss of choline acetyltransferase in the hippocampus and posterior cortex, and a significant reduction in hippocampal somatostatin. On the other hand, treatment with cysteamine significantly reduced the contents of somatostatin in all the brain regions examined, but minimally affected choline acetyltransferase activity. However, significant reduction in the striatal choline acetyltransferase activity and elevation in somatostatin content in the frontal cortex were found in aged rats compared with young rats. Taken together, these results strongly suggest that changes in the brain somatostatinergic transmission are involved in the cognitive deficits in the experimental animal models of dementia presently employed. Furthermore, the present comparative study further implies that there are differences in the relative involvement of the cholinergic and somatostatinergic systems in the performance of rats on two different tests of mnemonic function.
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PMID:Changes in brain somatostatin in memory-deficient rats: comparison with cholinergic markers. 764 25

Cholinergic markers, neuropeptides, and amines and their metabolites were sampled from identical specimens across 10 neocortical regions in a large sample of Alzheimer's disease (AD) cases and controls. Levels of choline acetyltransferase, acetylcholinesterase, somatostatin, corticotropin-releasing factor, serotonin, and 5-hydroxyindoleacetic acid were significantly reduced in AD versus controls. After data reduction, the most descriptive neurochemical indices were used to examine the relationship of neurochemical measures and dementia severity within the AD sample, controlling for age effects. Dementia severity ratings were based on antemortem assessments (46.9% of AD sample) and postmortem chart review (53.1% of the AD sample). Choline acetyltransferase activity was highly correlated with clinical dementia ratings across the neocortex of the AD cases. Somatostatin and corticotropin-releasing factor levels were correlated with dementia severity only when control cases were included in the analyses. None of the amines, their metabolites, or the neuropeptides quantified related significantly to dementia severity in the AD cohort. These data (a) confirm the strong association of cholinergic deficits with functional impairment in AD and show that this association is independent of age and (b) suggest that of all the neurochemical species quantified, the cholinergic indices may be unique in their association with dementia severity.
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PMID:Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits. 783 69

Ten patients with SDAT received the ECP therapy. The examination of Hasegawa's Dementia Scale (HDS), single photor emission computed tomography (SPECT) brain imaging, and some biochemical parameters in blood and CSF were selected to evaluate the effect of ECP for SDAT. After ECP treatment, the average HDS score of the patients increased, the value of P was close to 0.05; and the cortical cerebellar ratios of SPECT brain scan, the superoxide dismutase (SOD) activity and the concentrations of somatostatin-like immunoreactivity (SLI), dynorphin AL-13 (Dyn Al-13) in blood and/or CSF were significantly elevated. The results indicated that ECP could not only improve cerebral blood flow, but also make a notable impact on biological active substances in blood and CSF. It is suggested that ECP is beneficial to SDAT patients.
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PMID:Study of the external counterpulsation (ECP) therapy for senile dementia of the Alzheimer's type (SDAT). 783 2

Patients with Alzheimer's disease (AD) and major depression have been shown to have overlapping clinical symptoms and biological markers, including decreased concentrations of cerebrospinal fluid (CSF) somatostatin-like immunoreactivity (SLI), which may be related to alterations in the hypothalamic-pituitary-adrenal axis activity. As in prior studies, we found that CSF SLI was significantly decreased in a group of AD patients (N = 49) and a group of elderly patients with major depression (N = 18), as compared with 13 age-matched controls (F[2, 77] = 12.9, p < .001). In the present study, CSF SLI and CSF corticotropin-releasing factor correlated significantly within the group of AD patients (r = 0.49, p < .0004) and almost attained significance in the depressed patients (r = 0.47, p < .07). CSF SLI correlated significantly with urinary free cortisol within each patient group (r = -0.51, p < .03). Clinical measures of dementia severity and depression did not consistently correlate with CSF SLI in either patient group.
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PMID:CSF somatostatin in Alzheimer's disease and major depression: relationship to hypothalamic-pituitary-adrenal axis and clinical measures. 790 67

PSP is associated with a widespread cholinergic deficit likely corresponding to a loss in cholinergic neurons. The cholinergic damage dramatically affects the basal ganglia and specific cell groups of the mesencephalon and pons. This provides an anatomically defined basis for motor and supranuclear oculomotor syndromes characteristic of PSP. Unlike Alzheimer's disease and Parkinson's disease with dementia, the disease is not associated with a marked cholinergic deficiency in the cerebral cortex. Various peptides are present at normal concentrations in extrapyramidal and limbic subcortical areas in brains of patients with PSP. Of particular interest, is somatostatin, the levels of which are subnormal in cerebral cortex of patients with dementia of Alzheimer' or Parkinson's disease type.
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PMID:Cholinergic and peptidergic systems in PSP. 796 88

We studied the growth hormone (GH) response to GH-releasing hormone (GHRH) and the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in four groups of patients with dementia and examined whether GH and TSH secretion is altered in patients with Alzheimer's disease. The four groups included those with Alzheimer's disease (n = 28), parkinsonism with dementia (n = 10), progressive supranuclear palsy with dementia (n = 10), and dementia of vascular origin (n = 28). The results showed no differences among the four groups in GH response to GHRH (12.2 +/- 2, 10.7 +/- 2, 8.9 +/- 1.1, and 9.9 +/- 1.9 micrograms/ml, respectively); there was no correlation between GH response to GHRH and sex, stage of the disease, or cerebral atrophy. The proportion of patients with exaggerated, normal, or lower GH response was similar in the four groups in terms of TSH response to TRH (9.2 +/- 0.9, 11.1 +/- 1, 11.1 +/- 1, and 10.3 +/- 1 mU/ml, respectively), nor was there a correlation between TSH response to TRH and sex, stage of the disease, cerebral atrophy, or GH response to GHRH. The proportion of those with exaggerated, normal, or lower TSH response was similar in the four groups. Cerebrospinal somatostatin levels were similar in Alzheimer's disease and vascular dementia patients. These findings indicate that neither GH response to GHRH nor TSH response to TRH provides a useful diagnostic adjunct in Alzheimer's disease patients.
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PMID:Secretion of growth hormone and thyroid-stimulating hormone in patients with dementia. 798 74

Swollen, bulbous-shaped (dystrophic) neurites are a common pathologic feature of Alzheimer's disease (AD) and represent one of the most abundant neuritic abnormalities within the brains of patients with this disease. In the present study, we sought to determine whether the dystrophic neurites which are observed in association with senile plaques are unique to AD or whether they are characteristic of a more generalized process of neuritic and/or neuronal degeneration which can be observed in other neurodegenerative diseases. To accomplish this, we examined post-mortem brain material from patients with AD, Parkinson's disease (PD), Parkinson's disease with associated AD, Parkinson's disease with dementia yet without AD pathology, Huntington's disease (HD), Pick's disease and normal age-matched controls (NC). Using a battery of antibodies to amyloid beta-protein (A beta P), paired-helical filaments (PHF), tyrosine hydroxylase, substance P, neurotensin, and somatostatin we found that immunolabeled dystrophic neurites of the type characteristically observed in AD, were seen only in cases and in brain regions where A beta P deposition was present. More specifically, brain areas known to display severe afferent and/or local degenerative changes such as the caudate and putamen in all three PD groups, the caudate in the HD cases, and the temporal cortex in the HD and Pick's cases were conspicuously free of these swollen neurites unless A beta P deposition was also present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alzheimer's disease-like dystrophic neurites characteristically associated with senile plaques are not found within other neurodegenerative diseases unless amyloid beta-protein deposition is present. 809 26

There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer's disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age 65-75 years) and 15 AD patients (age 61-78 years), we studied the effects of both pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic somatostatin, on GH response to GHRH (1 microgram/kg i.v.). The GH response to PD alone was also studied. Twenty-two young healthy volunteers were studied as control group. Basal GH levels were similar in young, elderly and AD subjects (0.7 +/- 0.2, 0.8 +/- 0.2 and 0.9 +/- 0.2 microgram/l). IGF-I levels were lower (p < 0.005) in elderly (73.9 +/- 8.2 microgram/l) and in AD subjects (108.0 +/- 5.9 micrograms/l) than in young subjects (288.7 +/- 22.1 micrograms/l); however, they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD-induced GH release did not significantly differ in young, elderly and AD subjects while the GH responses to GHRH in the elderly (AUC: 297.9 +/- 49.2 micrograms/l) and in AD subjects (437.6 +/- 93.5 micrograms/l/h) were lower (p < 0.01) than in young subjects (658.6 +/- 100.1 micrograms/l/h). PD potentiated the GH response to GHRH both in elderly and in AD subjects (901.7 +/- 222.4 and 1,070.3 +/- 207.2 micrograms/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those recorded in young subjects (2,041.1 +/- 245.6 micrograms/l/h).(ABSTRACT TRUNCATED AT 250 WORDS)
Dementia
PMID:Growth hormone secretion in Alzheimer's disease: studies with growth hormone-releasing hormone alone and combined with pyridostigmine or arginine. 813 94

Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.
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PMID:Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention. 824 6

The two major primary degenerative dementias, dementia of Alzheimer type (DAT) and frontal lobe degeneration of non-Alzheimer type (FLD) have several clinical features in common but also many symptoms that differ. In a clinical material of 80 patients with either of the two forms of dementia (DAT = 39, FLD = 41) we have studied the levels of neuropeptides in the cerebrospinal fluid (CSF) in order to find biochemical markers for CNS affection. The dementia forms were evaluated by careful clinical analysis, psychometric testing and measurement of regional cerebral blood flow. Approximately one third of the subjects died during the completion of the study and neuropathology was performed, confirming the diagnoses. We observed reductions in the CSF levels of antidiuretic hormone and somatostatin in both DAT and FLD. A strong tendency to reduction was noted for neuropeptide Y (NPY). There was a correlation with the duration of disease demonstrating a significant reduction in NPY levels in subjects with DAT. Most notably there was a strong reduction in the levels of delta sleep inducing peptide (DSIP) in DAT cases only. The levels of DSIP in FLD were the same as in controls. The reverse was found for corticotropin releasing factor (CRF) which had a significant reduction in FLD patients but not in those with DAT. The present study indicates a difference in the CSF levels of neuropeptides, observations that these may serve as biochemical markers which differentiate DAT and FLD.
Dementia
PMID:Neuropeptides in cerebrospinal fluid of patients with Alzheimer's disease and dementia with frontotemporal lobe degeneration. 840 87


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