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)

Somatostatin-like immunoreactivity was measured in the CSF of 12 patients with Alzheimer's disease, 15 age-matched control subjects, and 20 older depressed subjects. Patients with dementia or depression were found to have lower CSF somatostatin concentrations than control subjects despite markedly different clinical presentations. Severity of depression was clearly different in all three groups but showed no significant correlation with CSF concentration of somatostatin. There was a significant positive correlation between CSF somatostatin-like immunoreactivity and cognitive functioning in all 47 subjects, but this association was not statistically significant within individual diagnostic groups. These data raise interesting questions about possible biological links between Alzheimer's disease and depression in older patients.
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PMID:CSF somatostatin in patients with Alzheimer's disease, older depressed patients, and age-matched control subjects. 288 77

Cerebrospinal fluid somatostatin and neuropeptide Y concentrations were measured in 26 healthy normal subjects, 27 patients with dementia of the Alzheimer type (DAT), and seven patients with DAT with extrapyramidal signs (EDAT). In healthy normal subjects, there was no significant correlation between age and either somatostatin or neuropeptide Y concentration. However, the concentrations of both peptides correlated significantly with each other. In patients with DAT and EDAT, the concentrations of somatostatin (17.5 +/- 5.0 and 16.4 +/- 5.0 pg/mL, respectively) were significantly reduced relative to age-matched control subjects (23.1 +/- 8.2 pg/mL) but were unrelated to dementia severity and did not change significantly during the progression of the disease. Neuropeptide Y concentrations did not differ significantly between the age-matched control, DAT, and EDAT groups (38.2 +/- 12.8, 37.0 +/- 12.3, and 30.3 +/- 7.8 pg/mL, respectively). These results suggest that in DAT, dysfunction of cortical somatostatin but not neuropeptide Y transmitter systems is reflected by reduced cerebrospinal fluid concentrations.
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PMID:Cerebrospinal fluid somatostatin and neuropeptide Y. Concentrations in aging and in dementia of the Alzheimer type with and without extrapyramidal signs. 289

Bethanechol chloride, a muscarinic agonist, was administered intrathecally to a sample of AD patients in double-blind crossover and open escalating-dose trials. There was a modest amelioration of disturbed behavior at a moderately high dose level, but no improvement in memory or cognition was seen at any dose. At the highest dose, cognition deteriorated. These findings, in conjunction with the results of the multicenter trial described by Harbaugh, suggest that the clinical efficacy of bethanechol in AD is limited. The disappointing results of trials with varied cholinomimetic therapies suggest that more than one biochemical abnormality is responsible for the AD dementia. The neuropeptide, somatostatin, is also reduced in AD, and the level of reduction is correlated with the degree of dementia. Manipulation of this transmitter, alone or in conjunction with acetylcholine, would appear to be a next logical step in the development of an effective neurotransmitter replacement therapy for AD. Implanted drug pumps will be needed for such clinical trials. The naturally occurring somatostatin-14 is not suitable because of its short half life. Sandostatin, an analog, is chemically stable and not metabolized by brain tissue. It does not cross the blood-brain barrier so that intrathecal administration is necessary. Pharmacological research in AD is complicated by a variety of psychometric problems including the criterion-related and construct validity of the outcome measures. Patients differ in their tolerance of various therapeutic agents and in the extent of the neurochemical pathology. It is critically important, therefore, to evaluate individual, as well as group, responses to treatment. The telephone log method may provide a useful way of generating enough observations for single subject analyses without overburdening the patient with repeated testing.
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PMID:New intrathecal drugs in Alzheimer's disease and psychometric testing. 289 28

Administration of hypothalamic peptides has been reported to induce behavioral changes and to modify neurological functions such as locomotor activity and learning. Somatostatin (SS) and growth hormone-releasing factor (GRF) exert opposite effects on anterior pituitary secretion. Similarly, at the central nervous system (CNS) level, SS and GRF display antagonistic actions on behavioral parameters. The authors were able to confirm these effects in male Wistar rats by means of a computerized electronic maze measuring locomotor activity and learning. SS concentration is reduced in specific areas of the CNS in patients with late onset of senile dementia of the Alzheimer's type (SDAT). In early onset SDAT a GRF test elicits a growth hormone response much greater than that observed in normal controls of the same age or in patients with late onset SDAT. Thus, administration of GRF to patients with early onset SDAT has been followed by a significant improvement in locomotion, appetite, mental performance and social interaction. A possible therapeutic role of GRF in the management of patients with dementia remains to be explored.
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PMID:Influence of somatostatin and growth hormone-releasing factor on behavior. Clinical and therapeutic implications in neuropsychiatric disorders. 290 Jan 93

A reduction in the levels of somatostatin-like immunoreactivity (SLI) and somatostatin binding sites in the cerebral cortex has been previously reported to occur in Alzheimer's disease (AD) and Parkinson's disease with associated dementia. In the present study, the levels of both SLI and high affinity [3H]somatostatin binding sites have been measured in the frontal (Brodmann area 9) and temporal (Brodmann area 21) cortices in patients with presenile and senile Alzheimer's disease, and in mentally normal and cognitively impaired cases of Parkinson's disease. The results were compared with those obtained from a group of normal patients matched for age and postmortem delay. No significant changes in SLI or somatostatin binding in the frontal and temporal cortex were found between any of the disease groups. These results suggest that involvement of the somatostatinergic system in AD or Parkinson's disease is not a consistent or primary neurochemical feature of these diseases.
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PMID:Cortical somatostatinergic system not affected in Alzheimer's and Parkinson's diseases. 290 99

Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in postmortem brain tissue from 12 control patients and 13 demented Parkinsonian patients who had Alzheimer-type cortical pathology. Twenty-two cortical regions were examined. Significant reductions in cortical SLI were found in 17 regions, while significant reductions in cortical NPYLI were found in nine regions. The reductions in SLI were typically 50-60%, while NPYLI reductions were 20-30%. These findings are similar to those in Alzheimer's disease (AD) and are consistent with a previous report of a dissociation between reductions in SLI and NPYLI in Parkinson's disease (PD) with dementia.
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PMID:Somatostatin and neuropeptide Y immunoreactivity in Parkinson's disease dementia with Alzheimer's changes. 290 67

Neuropeptides are widely distributed in the central nervous system, where they serve as neuroregulators. Recent interest has focused on their role in degenerative neurological diseases. We describe the normal anatomy of neuropeptides in both the cerebral cortex and basal ganglia as a framework for interpreting neuropeptide alterations in Alzheimer's disease (AD), Huntington's disease, and Parkinson's disease. Concentrations of cortical somatostatin are reduced in AD and in dementia associated with Parkinson's disease. Concentrations of neuropeptide Y and corticotropin-releasing factor are also reduced in AD cerebral cortex. The reduced cortical concentrations of somatostatin and neuropeptide Y in AD cerebral cortex may reflect a loss of neurons or terminals in which these two peptides are co-localized. In Huntington's disease, basal ganglia neurons in which somatostatin and neuropeptide Y are co-localized are selectively preserved. Cerebrospinal fluid concentrations of neuropeptides in AD reflect alterations in cortical concentrations. Improved understanding of neuropeptides in degenerative neurological illnesses will help define which neuronal populations are specifically vulnerable to the pathological processes, and this could lead to improved therapy.
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PMID:Neuropeptides in neurological disease. 294 36

Huntington disease is an autosomal dominant disorder that usually begins in mid-life and is characterized by progressive choreiform movements and dementia. Approximately 5% of patients develop symptoms prior to 14 years of age. In most juvenile cases, the gene is transmitted from the father. In children the clinical course is marked by mental deterioration or behavioral abnormalities, gait disturbances usually the consequence of rigidity, cerebellar signs, and seizures. The pathologic findings are highlighted by atrophy of the caudate. Atrophy also is observed on brain imaging, while positron emission tomography demonstrates marked caudate hypometabolism which antedates the appearance of the clinical disease. Cell death in the striatum primarily affects medium and small GABA-containing neurons, representing the striatal output projections. Somatostatin-containing neurons and cholinergic neurons are spared. The gene for Huntington disease has been localized in close proximity to the tip of the short arm of chromosome 4. The gene product and the manner by which it induces selective cell death is still unknown but should become evident in the near future.
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PMID:Huntington disease: finding the gene and after. 297 83

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

Psychopharmacology research in the dementia field is particularly difficult because there are no effective treatments on which to base models. Much effort is devoted to attempts to replace defective brain chemical transmitters or neuropeptides, with particular emphasis on the cholinergic system. There is also interest in noradrenaline, serotonin and somatostatin deficits. New directions include the study of glutamate-related excitotoxins such as quinolinic acid as possible causative agents for cerebral degeneration in dementia. Glutamate receptor antagonists, e.g. MK-801, may have the potential to limit or slow down neurodegenerative processes. Neurotrophic factors, e.g. nerve growth factor, may also possess the ability to protect neurons from irreversible loss.
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PMID:Test models and new directions in dementia research. 304 1


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