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)

Substance P (SP), Met-enkephalin (Met-enk) and cholecystokinin-8-S (CCK-8-S) were measured by a combined HPLC/RIA method in the caudate nucleus and anterior putamen from controls and from Parkinson's disease (PD) patients. SP levels were reduced in caudate in PD, but unchanged in putamen. No differences in Met-enk content were found in parkinsonians compared to controls. However, a significant correlation between DA and Met-enk levels in caudate nucleus from PD was observed. The concentration of CCK-8-S was unaltered in caudate nucleus or putamen in PD. The decrease in caudate nucleus SP levels might be related to the decrease in nigral SP levels in PD, while the reduction in Met-enk levels appears to be a feature of a subgroup of parkinsonian patients.
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PMID:Striatal neuropeptide levels in Parkinson's disease patients. 128 32

Immunoreactive neurokinin A was measured in the cerebrospinal fluid of twelve patients with Parkinson's disease and eleven normal subjects, using a sensitive and precise extraction/concentration radioimmunoassay method. The mean value obtained in Parkinson's disease patients (13.2 +/- 4.6 pmol/l) was lower than that of the controls (17.4 +/- 5.9). The tendency toward a significant decrease (p = 0.085) found in this preliminary study could indicate that neurokinin A containing neurons are involved in the pathophysiology of Parkinson's disease. In addition, the establishment of reference values for neurokinin A in cerebrospinal fluid may provide a basis for further studies of this neuropeptide in neurological disorders.
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PMID:Neurokinin concentrations in cerebrospinal fluid. A preliminary study in Parkinson's disease. 132 Sep 47

We designed this study to evaluate the expression of substance P (SP) in the striatum and the globus pallidus in normal controls, idiopathic Parkinson's disease (PD), and striatonigral degeneration (SND). We determined immunohistochemically the expression of SP in formalin-fixed, paraffin-embedded brain tissues using the free-floating method. In normal controls, we observed SP-like immunoreactivity in the internal segment of the globus pallidus, where the SP-positive fibers showed typical "woolly fiber" patterns. SP expression in the striatum had the characteristic patchwork of striosomes. Patients with PD showed the normal distribution pattern of SP. By comparison, in patients with SND, there was a striking diminution of SP in the putamen, while the SP-positive patches persisted in the caudate nucleus. This study represents the first unequivocal immunohistochemical demonstration of SP-positive striosomes in the human striatum.
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PMID:Striosomal organization of substance P-like immunoreactivity in parkinsonian patients. 137 45

The anatomy of melanin-containing neurons and other midbrain structures was examined by tyrosine hydroxylase (TH), calbindin D28k, and substance P immunostaining. Greater than 95% of cells in the substantia nigra pars compacta contained melanin, but densely packed cells in a ventral tier had a low content of melanin and loosely packed cells in a dorsal tier had a high content of melanin. Approximately 60% in the gamma group and 40% in the retrorubral nucleus had a low content of melanin. TH immunostaining was moderate in both the ventral and dorsal tiers, but more intense in the gamma group and retrorubral nucleus. Calbindin D28k was absent from the ventral and dorsal tiers, but present in the gamma group and retrorubral nucleus. In the light of primate tracing studies these findings suggest that the ventral tier of the pars compacta projects to striosomes of the striatum and the dorsal tier, gamma group and retrorubral nucleus to the matrix compartment. The ventral tier is more vulnerable than the dorsal tier in Parkinson's disease, but the cells contain less melanin. Neither tier contains calbindin D28k. This differential vulnerability between the ventral and dorsal tiers cannot be explained by melanin or calbindin D28k.
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PMID:Melanin, tyrosine hydroxylase, calbindin and substance P in the human midbrain and substantia nigra in relation to nigrostriatal projections and differential neuronal susceptibility in Parkinson's disease. 138 1

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle or of a sham lesion on the neuropeptide content of the striatum and substantia nigra was investigated with or without 6 months L-3,4-dihydroxyphenylalanine (L-DOPA; 200 mg/kg per day) plus carbidopa (25 mg/kg per day) treatment. [Met5]- and [Leu5]enkephalin, substance P (SP), neurotensin (NT) and cholecystokinin (CCK) were measured by a combined HPLC/RIA method. Neurotensin levels were increased in the striatum, and [Leu5]enkephalin, and SP levels were reduced in the substantia nigra as a consequence of the lesion, while the levels of other peptides were unaltered. Administration of L-DOPA to sham-operated rats bilaterally increased SP levels in striatum and substantia nigra, and [Met5]enkephalin and CCK content in substantia nigra. L-DOPA treatment of 6-OHDA-lesioned rats increased [Met5]- and [Leu5]enkephalin and CCK levels in the striatum ipsilateral to the lesion but not on the intact side. In the substantia nigra, the lesion-induced decrease in [Leu5]enkephalin and SP was reversed by L-DOPA treatment, [Met5]enkephalin and CCK levels ipsilateral to the lesion were further enhanced, and there was an increase in NT ipsilateral to the lesion. Cryptic [Met5]- and [Leu5]enkephalin increased in the ipsilateral striatum following an 6-OHDA lesion. L-DOPA treatment did not alter cryptic enkephalin levels or the lesion-induced increase in cryptic [Met5]enkephalin, while cryptic [Leu5]enkephalin was further increased in lesioned animals given L-DOPA. These results suggest that the pattern of change in basal ganglia peptides in Parkinson's disease is not due solely to the destruction of the nigrostriatal pathway, the drug treatment of the disease or a combination of these factors.
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PMID:Effects of a unilateral 6-hydroxydopamine lesion and prolonged L-3,4-dihydroxyphenylalanine treatment on peptidergic systems in rat basal ganglia. 138 71

Older patients who die with Parkinson's disease (PD) have fewer pigmented neurons in the locus coeruleus and fewer substance P-containing neurons in mesopontine tegmental nuclei. We analyzed two other medullary nuclei, the dorsal vagal nucleus and the hypoglossal nucleus, in eight PD patients and six normal controls by counting neurons in serial Nissl stained sections to determine the relationship between age at death and cell loss in these nuclei. PD-related neurodegenerative changes (Lewy bodies and neuronal loss) were present only in the dorsal vagal nucleus (13,637 +/- 1,323 neurons in PD, 24,885 +/- 1,157 in normal controls). Cells in the intermediate rostrocaudal part of the nucleus were most severely affected. There was a significant correlation between loss of vagal neurons and age at death in PD patients. No age-related cell loss was present in the dorsal vagal nucleus of normal brains, or in the hypoglossal nucleus in either PD or normal brains. These results confirm that age-related cell death depends on whether or not there is coexistent PD.
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PMID:Age-related loss of dorsal vagal neurons in Parkinson's disease. 143 19

The incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) among the Chamorros in Guam is remarkably high. The patients with ALS have clinical and pathological characteristics similar to those in other parts of the world. The PDC patients display parkinsonism and progressive dementia and show a characteristic neuronal loss in certain parts of the central nervous system such as the hippocampus and substantia nigra. The Guamanian patients with ALS and PDC commonly have widespread Alzheimer's neurofibrillary changes, but without the associated senile plaques. We have applied immunohistochemical procedures to examine the expression of marker substances in Guamanian ALS and PDC. The markers studied include tau protein, ubiquitin, beta proteins, synaptophysin, calcineurin, Met-enkephalin, substance P and tyrosine hydroxylase. The results were compared with the findings in patients with Alzheimer's disease, Parkinson's disease, sporadic ALS and familial ALS.
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PMID:Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies. 158 17

Using postmortem immunohistochemical analysis, we have identified degeneration of several different neuronal cell groups in the brainstem of patients dying with idiopathic Parkinson's disease. We report the first chemically identified loss of presumed serotonin neurons in the median raphe nucleus of the pons and of substance P-containing preganglionic neurons in the dorsal motor vagal nucleus. This evidence is concordant with other evidence that the primary neuropathological process is not confined either to a single pathway or to neurons containing a particular transmitter. Rather it appears that Parkinson's disease affects several classes of neurons in localized areas of the brainstem.
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PMID:Loss of brainstem serotonin- and substance P-containing neurons in Parkinson's disease. 169 Oct 42

A comparative topographical immunohistochemical analysis was performed on the basal ganglia (including the substantia nigra) in Guamanian parkinsonism-dementia complex, idiopathic Parkinson's disease (PD), and Alzheimer's disease (AD). The striatal projection neurons and their efferent fibers were examined by using antibodies to calcineurin, methionine-enkephalin, and substance P. Tyrosine hydroxylase served as a marker for nigrostriatal dopaminergic neurons. The basal ganglia of patients with parkinsonism-dementia complex reacted strongly with all of the antibodies and the reaction products exhibited a normal distribution pattern. These findings suggest that the striatal output system is well preserved in patients with this disease. Similar results were obtained in patients with AD or PD. However, as compared to the patients with AD or PD, patients with parkinsonism-dementia complex showed severe reduction (greater than 90%) in the number of dopaminergic neurons in both the lateral and the medial portions of the substantia nigra. In view of the functional cortico-subcortical loops, these findings could explain the parkinsonian features and in part the cognitive impairment that occur in parkinsonism-dementia complex on Guam.
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PMID:Immunohistochemical study of the striatal efferents and nigral dopaminergic neurons in parkinsonism-dementia complex on Guam in comparison with those in Parkinson's and Alzheimer's diseases. 169 18

Substance P-like immunoreactivity (SPLI) was determined in cerebrovascular fluid of patients with extrapyramidal motor diseases. Patients with Parkinson's disease (PD) showed a SPLI concentration decreased by 30% compared with patients without extrapyramidal disease. No differences were apparent for patients with dystonia. Fluid obtained from the foramen Monro showed higher SPLI concentrations than fluid from a lateral ventricle, indicating that hypothalamic sources are important for ventricular substance P. Lateral ventricular SPLI was particularly low in parkinsonian patients which raises the possibility of a decreased SPergic activity in basal ganglia occurring in PD.
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PMID:Ventricular fluid neuropeptides in Parkinson's disease. II. Levels of substance P-like immunoreactivity. 170 13


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