Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Somatostatin-like immunoreactivity levels (SLI) in cerebrospinal fluid (CSF) were determined in twenty-three patients with untreated parkinsonian syndrome (15 with Idiopathic Parkinson's disease (IPD) and 8 with other forms of parkinsonism) at the moment of clinical diagnosis (mean duration of disease 1.1 +/- 0.2 years), and in 26 subjects without neurological symptoms. None of the IPD patients had a diagnosis of dementia at the moment of inclusion in the study. CSF-SLI content was found to be significantly higher in patients with parkinsonian syndrome (107.9 +/- 9.8 pg/ml) than in control subjects (73.5 +/- 8.4 pg/ml). The increase was also significant when controls were compared with IPD patients. In addition, a positive correlation between SLI and homovanillic acid was found in CSF of all patients. A test of learning memory was used to evaluate the mental state of patients and a significant increase in CSF-somatostatin levels was observed in patients with Idiopathic Parkinson's disease and severe affectation of memory. These results indicate that in the early steps of untreated parkinsonian syndrome, somatostatin concentration in cerebrospinal fluid may increase, probably due to the neurodegenerative depletion of somatostatin from striatal or cortical neurons.
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PMID:CSF somatostatin increase in patients with early parkinsonian syndrome. 852 3

There is some evidence that Parkinson's disease (PD) seems to be a heterogenous and generalized brain disorder reflecting a degeneration of multiple neuronal networks, including somatostatinergic neurons. Somatostatin-like immunoreactivity (SLI) and its molecular forms, high molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-25/28) and Des-ala-somatostatin (Des-ala-SST), as well as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated using HPLC and radioimmunoassay in the cerebrospinal fluid (CSF) of 35 aged parkinsonian patients with different stages of intellectual deterioration. The influence of L-dopa-treatment on these neurochemical parameters was evaluated. Without a correlation with dementia scores (p = 0.11), SLI was significantly reduced in PD in comparison to the control group (p < 0.05). The reduction was related to the progression of the disease. Correlations between SLI, HVA and 5-HIAA indicate a heterogenous brain disorder in PD with alterations of several transmitter systems and functions. Complex qualitative and quantitative changes in the molecular pattern of SLI are compatible with a dysregulated synthesis and/or posttranslational processing. L-dopa-treatment was associated with a significant increase of HVA (p < 0.05) and HMV-SST (p < 0.05) and a slight, but insignificant increase of SLI (p = 0.11).
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PMID:Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease--effect of L-Dopa. 881 4

In order to gain a better insight in the serotonergic disorder affecting the parkinsonian brain, the growth hormone (GH) response to the 5-HT 1 serotonergic receptor agonist sumatriptan was tested. Sumatriptan was injected subcutaneously in 10 de novo parkinsonian patients (aged 58-69 years) and in 9 age-matched normal controls. On different occasions, subjects were also tested with GH-releasing hormone (GH-RH; 1 micrograms/kg body weight in an intravenous bolus) and L-arginine (30 g in 50 ml normal saline over 30 min), which releases GH from somatostatin inhibition, to determine whether GH secretion in response to alternate secretagogues is preserved in Parkinson's disease. In addition, a control test with the administration of normal saline instead of drug treatments was performed. Plasma GH levels were recorded over 2 h in all tests. Placebo administration did not change plasma GH levels in any subject. Similar GH responses were observed in normal controls and parkinsonian patients when GH-RH or arginine were administered. A significant GH increase was observed in normal controls after sumatriptan injection; in contrast, GH secretion was not modified by sumatriptan administration in parkinsonian patients. These data show that Parkinson's disease is associated with an impairment in the 5-HT1-receptor-mediated serotonergic transmission in the control of GH secretion, suggesting that this specific defect might alter other serotonergic-mediated mechanisms in the parkinsonian brain.
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PMID:Defective 5-HT 1-receptor-mediated neurotransmission in the control of growth hormone secretion in Parkinson's disease. 909 98

Levels of the neurotransmitter somatostatin (SS) have previously been shown to be reduced in the cortex and hippocampus of demented parkinsonian patients and patients with Alzheimer's disease. In situ hybridisation histochemistry (ISHH) was performed with an 35S tail-labelled oligonucleotide DNA probe to human SS mRNA, to examine its expression within the striatum, medial medullary lamina (MML) and reticular thalamic nucleus in Parkinson's disease (PD) and in matched controls. A chronic unilaterally MPTP-lesioned L-DOPA-naive primate model was also examined for comparison of SS mRNA expression with that in human L-DOPA treated PD subjects. Quantitation of SS mRNA expression on emulsion dipped sections revealed a significant increase (82%) in the MML of the globus pallidus in PD (56.5 microm2 of silver grain/cell, n = 9 cases) compared to controls (26.3 microm2/cell, n = 13 cases, p < 0.01, Student's t-test), paralleling the increase previously observed by this group for NOS mRNA. SS mRNA expression was higher in the dorsolateral than ventromedial putamen in controls (p < 0.001; DL: 24.89 +/- SEM 1.35; VM: 17.96 +/- SEM 2.63; n = 14) but this gradient was lost in PD cases (p > 0.05; DL: 22.68 +/- 1.94; VM: 22.17 +/- 2.94; n = 10). These findings suggest specific modification of basal ganglia SS-ergic pathways in PD.
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PMID:Selective increase in somatostatin mRNA expression in human basal ganglia in Parkinson's disease. 940 18

Although neuritic and diffuse plaques generally coexist in Alzheimer disease (AD) neocortex, the predominance of diffuse plaques in the striatum prompted us to explore the potential influence of striatal features such as the striatal mosaic on beta-amyloid (A beta) deposition. Using double immunohistochemistry with an antibody to A beta in combination with antibodies to met-enkephalin or somatostatin, we investigated the relationship between diffuse plaques and neuropeptide distribution in the dorsal striatum. This relationship was examined in "pure" AD cases as well as in AD cases with coexisting Parkinson disease (PD) pathology, i.e. nigral degeneration and Lewy bodies at any site (AD + PD). Despite the presence of numerous A beta-positive diffuse plaques in both groups, the mosaic pattern, as exemplified by met-enkephalin-immunoreactive patches, was preserved. No obvious association was observed between the plaques and met-enkephalin-positive patches or somatostatin-immunoreactive neurons. Tyrosine hydroxylase immunoreactivity in the matrix was, however, diminished in AD + PD, most likely reflecting the nigral degeneration in these cases. Overall, these observations suggest that neostriatal A beta deposition in AD is not influenced by environmental factors associated with the striatal mosaic.
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PMID:Diffuse plaques in the striatum in Alzheimer disease (AD): relationship to the striatal mosaic and selected neuropeptide markers. 941 85

Brain-derived neurotrophic factor (BDNF) modulates neuropeptide levels in hippocampus and cortex of young adult rats. Neuropeptide levels are altered in some age-related disorders, such as Alzheimer's and Parkinson's Disease. BDNF may be able to rectify peptide abnormalities but, because plasticity decreases with age, BDNF may not alter peptide levels as readily in aged animals. To determine if BDNF would regulate peptide levels in aged rats, young, aged memory-impaired, and unimpaired rats were infused with BDNF or vehicle into hippocampus and cortex. Cell profile counts, cell profile areas, fiber counts, and/or fiber terminal densities were measured for sections immunostained for neuropeptide Y (NPY), somatostatin (SOM), cholecystokinin-8 (CCK), and dynorphin A(1-8) (DYN). Results showed that BDNF upregulated cortical NPY-immunoreactivity (ir) and SOM-ir, upregulated hippocampal NPY-ir, and downregulated hippocampal DYN-ir in both aged and young rats. In addition, BDNF significantly and selectively normalized the areas of atrophied deep cortical CCK-ir cell profiles in aged-impaired rats. Finally, decreased CCK-ir fiber density was found in the hippocampal formation of aged memory-impaired rats.
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PMID:Peptide immunoreactivity in aged rat cortex and hippocampus as a function of memory and BDNF infusion. 1054 80

Somatostatin may play a role in several neuropsychiatric disorders, including Parkinson's disease. Although functional interactions between somatostatinergic and dopaminergic transmitter systems have been well documented, no study has been conducted in animals with experimental Parkinsonism to explore the effects of somatostatin on dopamine receptor-mediated behavior. In the present study, rats with unilateral 6-hydroxydopamine-induced destruction of the medial forebrain bundle were assessed following administration of the dopamine(1/2) receptor agonist apomorphine. Ipsilateral intrastriatal infusion of somatostatin produced a dose-related inhibition of apomorphine-induced rotations with maximal effect at a dose of 7.5 microg in 2 microl. This inhibitory effect of somatostatin was antagonized by the somatostatin antagonist cyclo-somatostatin (0.1 microg in 2 microl, intrastriatally). Neither somatostatin (up to 15 microg in 2 microl) nor cyclo-somatostatin on its own induced rotations; similarly, this dose of cyclo-somatostatin did not affect apomorphine-induced rotations. From these results we suggest that exogenous somatostatin, by directly acting on its specific receptors in the striatum, inhibits the effects of dopamine receptor activation in parkinsonian rats. We conclude that therapies based on modulation of somatostatin may be worth exploring in the management of Parkinson's disease and other disorders of the basal ganglia.
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PMID:Somatostatin modulates the behavioral effects of dopamine receptor activation in parkinsonian rats. 1204 44

High levels of neuropeptide Y (NPY) are found in basal ganglia where it is co-localised with somatostatin (SOM) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH/d) in a population of striatal GABA containing interneurones. Although alterations occur in the levels of various neuropeptides in basal ganglia in Parkinson's disease (PD), it is not known whether NPY is affected. Using in situ hybridisation immunohistochemistry, we have examined the distribution of NPY mRNA in the caudate nucleus, putamen and nucleus accumbens of normal individuals and patients with PD. NPY mRNA was weakly expressed in the caudate nucleus, putamen and nucleus accumbens in normal individuals with a scattered labelling of neurones. However, there was no regional localisation within any brain area and no obvious differences between brain regions. In PD, the number of NPY mRNA-expressing cells was increased as was the density of the silver grains overlying each positive cell. The increase was more pronounced in the nucleus accumbens and in the ventral part of the caudate nucleus. The increase in NPY mRNA expression observed in patients with PD may reflect the loss of dopaminergic tone on striatal NPY containing interneurones, although a role for chronic L-DOPA therapy cannot be ruled out.
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PMID:Increased neuropeptide Y mRNA expression in striatum in Parkinson's disease. 1259 Nov 54


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