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

Neurotensin receptor autoradiography reveals dense binding in normal human substantia nigra. In nigra from patients with Parkinson's disease, nigral receptor binding is only about one-third of control values. 'Saturation' analysis suggests that these changes result from receptor loss. These results support a neurotensin-dopamine interaction in human nigro-striatal circuits.
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PMID:Parkinson's disease: depletion of substantia nigra neurotensin receptors. 608 53

In Huntington's disease, there is a decrease of the neuropeptides, substance P, enkephalins, and cholecystokinin in the striatonigral system, whereas in Parkinson's disease an increase of substance P is found in the substantia nigra. Several neuropeptides should be involved in Alzheimer's disease: substance P, endorphins, vasopressin, ACTH, somatostatin, vasoactive intestinal peptide, cholecystokinin, neurotensin, delta sleep-inducing peptide. Alterations of substance P, vasoactive intestinal peptide, cholecystokinin, somatostatin, and endorphins may be related to the pathophysiology of schizophrenia. Delta sleep-inducing peptide may interfere in addiction pathology.
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PMID:Putative peptide neurotransmitters in human neuropathology: a review of topography and clinical implications. 618 57

Drug addicts abusing heroin substitutes contaminated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and perhaps those who work with this substance, may develop symptoms similar to those seen in Parkinson's disease [7, 12, 13]. We describe the results of a study in which rats were given daily injections of MPTP for two weeks. A progressive suppression of activity was seen, but the subjects rapidly recovered when treatment ceased. The animals were then injected with D-amphetamine or apomorphine; the former drug enhanced activity, to levels seen in control (non-MPTP treated) subjects. Apomorphine had no effect, either on control or MPTP-treated subjects. The effects of acute (0, 2.5, 5.0 and 10.0 mg per rat) administration of MPTP were also studied. The two lower doses significantly decreased activity, but the highest dose did not. Histological examination showed that 2 weeks' treatment with MPTP did not produce neuronal degeneration in the pars compacta of the substantia nigra (SN). In these animals, there were no changes in levels of dopamine, 5-hydroxytryptamine, or their metabolites in either the SN or the caudate nucleus. MPTP had no effect on the levels of neurotensin, somatostatin and substance P in several brain areas. It is concluded that MPTP has reliable effects on locomotor activity in rats without producing measurable histological or neurochemical changes in the nigrostriatal dopaminergic system.
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PMID:N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) affects locomotor activity without producing a nigrostriatal lesion in the rat. 633 3

Neurotransmitter receptors and neurotransmitter transporters were studied postmortem in the brains of 9 PSP patients by receptor autoradiography. Densities of dopamine uptake sites and neurotensin receptors were significantly reduced in striatum and substantia nigra consistent with a localization of these binding sites on degenerating dopaminergic nigrostriatal projection neurons. The densities of dopamine D1 receptors were unchanged. Dopamine D2 receptors were unaltered when labeled by [125I]-Iodosulpride or [3H]-CV 205 502, but appeared to be significantly reduced when labeled by [3H]-spiperone. Levels of D2 mRNA were comparable to control levels, suggesting that only subtypes of Dopamine D2-like receptors may be affected in PSP. Serotonin (5-HT) uptake sites and 5-HT receptors were not altered. The density of muscarinic receptors was reduced in striatum, possibly related to a degeneration of cholinergic striatal interneurons, but increased in internal globus pallidus. GABAA/BZ receptor binding sites were significantly reduced in both segments of globus pallidus, probably as a consequence of severe degeneration of intrinsic pallidal neurons in PSP. Binding of substance P in striatum tended to be decreased but failed to reach statistical significance. Compared to Parkinson's disease, the densities of more neurotransmitter receptors were altered in PSP. With the exception of increased muscarinic receptor binding sites in medial globus pallidus, the alterations seen in PSP seem to reflect cell loss rather than functional changes.
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PMID:Alterations of neurotransmitter receptors and neurotransmitter transporters in progressive supranuclear palsy. 752 68

We have recently cloned the neurotensin receptor from human substantia nigra. Using in situ hybridization techniques, with an 35S-labeled antisense RNA probe complementary to this receptor complementary DNA, we studied the expression of the human neurotensin receptor in the brain from control and Parkinson's disease subjects. We also performed an analogous study with rat brain. Neurotensin receptor messenger RNA was present in high levels in melanized neurons of the substantia nigra pars compacta and the nucleus paranigralis (the ventral tegmental area for rat brain). Background levels of signals for neurotensin receptor messenger RNA were detected in the nucleus ruber, the colliculus inferior and the striatal subdivisions (the nucleus caudatus, the putamen and the nucleus accumbens) of both human and rat brain. All these areas, except the nucleus ruber and the collicus inferior, contain very high to high levels of neurotensin receptor binding sites. Additionally, Parkinson's disease brains had markedly fewer melanized (possibly dopaminergic) neurons, as expected, and correspondingly very low or background levels of messenger RNA for neurotensin receptor. We have also demonstrated heterogeneity among the melanized cells expressing messenger RNA encoding the neurotensin receptor in the substantia nigra and the nucleus paranigralis of human brain. The neurons in the nucleus paranigralis had lower melanin pigmentation and higher expression of neurotensin receptor messenger RNA. In general, the expression of the messenger RNA within the highly and evenly melanized neurons was lower than that found in low or unevenly pigmented neurons. The neurons in the nucleus paranigralis had lower melanin pigmentation and higher expression of neurotensin receptor messenger RNA. The low pigmented neurons in the ventral tier of the substantia nigra had relatively high expression. On the other hand, highly and evenly melanized neurons in these regions of the brain had low expression of neurotensin receptor messenger RNA. Together with the previous binding data, it is suggested that not only in rat brain, but also in human brain, melanized (possibly dopaminergic) neurons in the substantia nigra and the nucleus paranigralis (ventral tegmental area of rat brain) synthesize neurotensin receptors and express them in their perikarya and the terminal regions. Additionally, the heterogeneity of the melanized neurons in human brain may play a role in the normal function of dopaminergic systems and probably in the etiology of some neurological and psychiatric disorders.
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PMID:Heterogeneity of melanized neurons expressing neurotensin receptor messenger RNA in the substantia nigra and the nucleus paranigralis of control and Parkinson's disease brain. 770 May 29

A method that combines high performance liquid chromatography with radioimmunoassay (HPLC/RIA) has been used to characterize neurotensin-like immunoreactivity (NT-IR) in the basal ganglia from control subjects and Parkinson's disease (PD) patients. In samples from the caudate nucleus and putamen, NT-IR eluted as two HPLC peaks. One was indistinguishable from the synthetic tridecapeptide, while the other peak corresponded to oxidized NT, as judged by its chromatographic behaviour and its reaction with the antiserum employed. There were marked discrepancies between the IR detected in crude extracts and that in HPLC purified samples. NT levels (HPLC/RIA) were unaltered in the caudate nucleus, putamen and both segments of the globus pallidus in the parkinsonian brain. In contrast, there was a two-fold increase in NT content in both zona compacta and zona reticulata of the substantia nigra in PD patients compared to controls. Degeneration of the nigrostriatal pathway and/or prolonged antiparkinsonian treatment in PD appears to alter neurotensin levels in an attempt to activate the dopaminergic nigrostriatal pathway.
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PMID:Characterization of neurotensin-like immunoreactivity in human basal ganglia: increased neurotensin levels in substantia nigra in Parkinson's disease. 778 65

The specific binding of [3H]neurotensin, [3H]substance P, [3H]D-Ala2-D-Leu5-enkephalin (delta receptors) and [3H]-Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (mu receptors) were studied in membrane preparations of caudate nucleus, putamen, globus pallidus and substantia nigra from patients with Parkinson's disease and from age-matched controls. The density of neurotensin receptors was decreased in globus pallidus (lateral and medial segments) in parkinsonian brain. Substance P receptors were reduced in the putamen (anterior and posterior) and in lateral globus pallidus in Parkinson's disease. There was a reduction in the density of opioid receptors in posterior putamen and in mu receptors in caudate nucleus and putamen (anterior and posterior). No differences in neuropeptide receptor binding were observed in substantia nigra from parkinsonian brains compared with control subjects. The reductions in neuropeptide receptor density were less marked than the decrease in caudate and putamen content of dopamine and its metabolites. This suggests that neuropeptide receptors are only partially localized to striatal dopamine terminals.
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PMID:Neurotensin, substance P, delta and mu opioid receptors are decreased in basal ganglia of Parkinson's disease patients. 796 97

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

The effect of neurotensin (NT) on the release of acetylcholine (ACh) and dopamine (DA) from striatal slices of the rat brain was studied. Neurotensin, 1-150 nM, was able to release ACh from cholinergic interneurons of the striatum. Like the response to electrical stimulation, the ACh-releasing effect of NT was completely inhibited by tetrodotoxin indicating that neuronal firing is involved in its effect. Immunneutralization reduced the stimulation-evoked release of ACh, an effect that was much marked when the inhibitory dopaminergic input was suspended by sulpiride-selective antagonists of D2 receptors. Sulpiride, 0.1 mM, induced a 2-fold increase in the NT- and electrically-induced release of ACh. A quantitatively similar increase was also observed after degeneration of the nigrostriatal DA pathway with 6-hydroxydopamine (6-OHDA) (2 x 250 micrograms/animal, i.c.v.). However, the D2 receptor agonist quinpirole, 0.01 mM, significantly reduced the NT-induced release of ACh by 77%. Neurotensin enhanced the stimulation-evoked release of [3H]DA. These findings indicate that, using field stimulation when dopaminergic, cholinergic and NT-containing neurons are stimulated in concert, NT is capable of releasing both ACh and DA in the striatum, but its effect on ACh release is masked unless the D2 receptor-mediated tonic inhibitory effect of DA released from the nigro-striatal pathway is attenuated. Thus, in Parkinson's disease where the dopaminergic input is impaired, NT may be involved in producing cholinergic dominance.
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PMID:Effect of neurotensin and immunneutralization with anti-neurotensin-serum on dopaminergic-cholinergic interaction in the striatum. 810 Nov 33

Superoxide dismutase (SOD) plays an important role in the protection of cells against the deleterious effects of free radicals by dismutating the toxic superoxide anion radical. Although oxygen-based radicals have been implicated in the process of aging and in neurodegenerative disorders such as Parkinson's disease, the contribution of these free radicals to the pathology of these entities has yet to be clarified. It is also not certain that increased levels of free radical scavenging enzymes would attenuate the molecular and cellular processes that lead to these pathological states. In order to assess the contribution of increased SOD gene dosage to the pathogenesis of Down's syndrome, transgenic mice have been constructed that overexpress the human CuZnSOD. We are also using this model to evaluate the role of free radicals in age-associated changes in brain neurotransmitters and their receptors. In the present study, transgenic mice and their nontransgenic littermates, aged 6 weeks and 21 months, were used in an autoradiographic receptor study of the distribution of brain neurotensin receptors. At 6 weeks of age, there were no significant differences between the two groups of mice in most brain regions. In addition, [3H]NT binding sites showed parallel age-related decreases in the majority of the areas examined in both groups. However, significant age-related decreases in the septum, the diagonal band of Broca, and in some subdivisions of the caudate-putamen were observed only in SOD-Tg mice. In contrast, significant age-related decreases in the core area of the nucleus accumbens and the dorsal aspect of the dentate gyrus of the hippocampus were seen only in non-Tg mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoradiographic distribution of [3H]neurotensin receptors in the brains of superoxide dismutase transgenic mice. 839 Jan 6


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