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)

Dopamine-3-O-sulfate (DA-3-O-S) and dopamine-4-O-sulfate (DA-4-O-S) are important end products of L-dopa metabolism. Therefore they may give indications of disturbances in the peripheral metabolism of catecholamines, when measured in urine samples of patients with Parkinson's disease (PD). In addition, information about the reliability of DA sulfatation after L-dopa therapy may be of significance for its role in the elimination of DA from the peripheral nervous system. Although DA-3-O-S appears to be the predominant sulfo-conjugate in urine, there are no changes in PD nor in depression syndrome compared to controls with or without other neurological disorders. By contrast, DA-4-O-S is significantly decreased in de novo PD subjects. However, a similar reduction is notable in patients with other neurological disorders. In depressed persons the loss of this compound was less pronounced as compared to de novo PD. Treatment with combined L-dopa therapy caused increased excretion of DA-3-O-S, while changes in DA-4-O-S were only marginal. It is concluded that urinary DA-3-O-S cannot be used as marker for PD, while DA-4-O-S is significantly reduced in a variety of neurological disorders and in particular in de novo PD. Further studies are necessary to elucidate its role as possible peripheral marker to distinguish preclinical PD and depression syndrome.
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PMID:Urinary dopamine sulfate: regulations and significance in neurological disorders. 208 10

Free radicals generated from oxidation reactions may contribute to the pathogenesis of Parkinson's disease (PD). Free radicals are capable of reacting almost instantaneously with membrane lipids and causing lipid peroxidation, membrane injury, and cell death. Dopamine is metabolized by oxidation reactions capable of generating free radicals. Recent evidence indicates that the substantia nigra of patients with PD contains increased iron, which enhances oxidation, and decreased glutathione, which protects against the formation of free radicals. Further, the end products of lipid peroxidation are increased in the substantia nigra of patients with PD, supporting the notions that free radicals are being generated and may contribute to dopamine neuronal death. This hypothesis suggests that antioxidant therapies may slow the rate of progression of PD and raises concern that metabolites of levodopa therapy may accelerate the rate of neuronal degeneration.
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PMID:Oxidation reactions in Parkinson's disease. 221 72

Associations between hyperthyroidism and Parkinson disease have been reported. The treatment of the hyperthyroid state seems to improve the extrapyramidal symptomatology. We report a case of a woman suffering from Parkinson disease and hypothyroidism. The treatment with thyroxine increased parkinsonian tremor. Dopamine regulation of TSH circadian and pulsatile release is not clear. These observations stress the possible role of thyroid hormones in regulating dopaminergic metabolism.
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PMID:[Dysthyroidism and Parkinson's disease]. 222 22

Dopamine and it metabolites dihydroxyphenylacetic acid and homovanillic acid were measured in the retinas of eight patients with Parkinson's disease who died. They were divided into two groups according to their last dose of levodopa therapy. One group of three patients had not received levodopa therapy for at least 5 days before death, and the other group of five patients had received therapy 2-15 hours before death. Each patient was matched with controls for delay between death and freezing. In the three patients without levodopa therapy, the retinal dopamine content was lower than normal. In the five patients who received levodopa therapy before death, the retinal dopamine content was similar to that in the controls. This study is the first direct evidence to the authors' knowledge that retinal dopamine concentration is decreased in Parkinson's disease, as it is in the nigrostriatal pathway.
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PMID:Decreased dopamine in the retinas of patients with Parkinson's disease. 224 12

Microdialysis in the human brain has been performed for the first time during thalamotomy intended to relieve tremor in patients with Parkinson's disease. The aim was to test the reliability of the microdialysis technique for biochemical characterization of a target area in the human brain during a routine operation. Microdialysis probes were introduced through the same trajectory as the lesioning electrode thus causing no additional damage to the brain. Dopamine, DOPAC, HVA, 5-HIAA, hypoxanthine, inosine, guanosine, adenosine, GABA, taurine, aspartate and glutamate were measured in the perfusate from the target region - the Vim nucleus. The results show initial high levels that reach baseline levels after 10-20 minutes. Surprisingly, consistent and reproducible levels were found, the only exception being one patient on 1-DOPA therapy who had elevated DA and metabolite levels.
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PMID:Microdialysis in the human brain: extracellular measurements in the thalamus of parkinsonian patients. 230 73

Dopamine (DA) and homovanillic acid (HVA) concentrations were measured in subregions of substantia nigra, ventral tegmental area and retrorubral field in vervet monkeys 1 to 2 months after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Identical MPTP treatment regimens produced animals with different degrees of parkinsonism. In asymptomatic monkeys, changes in DA and HVA concentrations in the midbrain DA regions were relatively small and involved central substantia nigra and dorsomedial ventral tegmental area. In contrast, changes in symptomatic monkeys were more severe and widespread, significantly affecting all examined subregions of substantia nigra (greater than 75% DA depletion), both dorsomedial and ventromedial ventral tegmental area and lateral, but not medial, retrorubral field. The data indicate that DA neurons in subregions of substantia nigra, ventral tegmental area and retrorubral field are not equally susceptible to MPTP toxicity. The pattern of MPTP-induced DA and HVA losses in the vervet monkey mesostriatal dopaminergic system may resemble postencephalitic Parkinson's disease more closely than idiopathic Parkinson's disease.
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PMID:MPTP-induced parkinsonism: relative changes in dopamine concentration in subregions of substantia nigra, ventral tegmental area and retrorubral field of symptomatic and asymptomatic vervet monkeys. 235 Jul 2

In immunocytochemical studies, the CSF from Parkinson disease (PD) patients and from Alzheimer disease (AD) patients were investigated for the presence of neuron specific antibodies using dopaminergic and cholinergic neuronal cultures from embryonic rat brain, respectively. Dopamine containing cell bodies were labelled by Parkinsonian CSF-IgG, while cholinergic neurons, identified with a-NGF-receptor antibodies, were recognized by CSF from AD-patients. The CSF from PD-patients was investigated after autologous adrenal transplantation. CSF was removed 7 d, 5 months and 1 year after operation. When added to 18 d neuronal cultures for 3 d, the 7 d CSF caused neuronal cell and a glial reaction. The 4 months CSF caused cell death, but markedly less than the 7 d CSF. One year after transplantation the CSF had no toxic effects; these cultures were similar to control cultures. It is concluded that CSF from PD patients may contain aggressive IgG-species specific for DA neurons, and that the amount of such antibodies decrease after adrenal transplant operations. It is suggested that neurodegenerative diseases may become aggravated by autoimmune reactions.
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PMID:Investigations on auto-antibodies in Alzheimer's and Parkinson's diseases, using defined neuronal cultures. 235 1

I studied the neuropsychiatric disorders occurring after overdose with manganese (Mn), which have been shown to be neurologically similar to Parkinson's disease. MnCl2 doses of 10 mg Mn/kg, administered a total of 15 times, were injected intraperitoneally into rats. Then I determined the concentration of monoamines, their metabolites and the activity of catecholamine-related enzymes of the rat brain using high-performance liquid chromatography (HPLC). 1) In the Mn-loaded rats, the concentration of dopamine (DA) was significantly decreased in the nucleus caudatus-putamen (C/P)(p less than 0.05), the thalamus (p less than 0.05) and in the mesencephalon (ME) (p less than 0.001), while that of homovanillic acid decreased in the C/P (p less than 0.05). The concentration of norepinephrine (NE) was decreased in the hypothalamus (p less than 0.01) and that of 3-methoxy-4-hydroxyphenyl-glycol was decreased in the C/P (p less than 0.001) and in the thalamus (less than 0.05); however serotonin and 5-hydroxyindoleacetic acid concentrations showed no variation from those of the controls. 2) As for the enzymes of catecholamine biosynthesis, tyrosine hydroxylase (TyrOHase) activity was increased in the hypothalamus (p less than 0.05) and was reduced in the ME (p less than 0.01). Dopa decarboxylase activity showed no change. Dopamine-beta-hydroxylase (DBH) activity was reduced in the C/P and the thalamus (p less than 0.05 respectively). Phenylethanolamine-N-methyltransferase activity was detected in the hypothalamus, the ME, and at low levels in the thalamus (p less than 0.01). Among the enzymes of catecholamine metabolism, catechol-O-methyltransferase activity showed no variation, but monoamine oxidase (MAO) type-a and type-a + b activities were significantly increased in the cerebral cortex (p less than 0.01), and MAO type-a + b as significantly reduced in the C/P and the hypothalamus (p less than 0.01). The decrease on DA and NE contents found could be due to the reduction of such biosynthesizing enzymes as TyrOHase and DBH. Especially, the DA content was markedly decreased in the ME, found mostly in regions where DA neurons originate. Thus the variation of this region would be the first disorder. And it was interesting to note that MAO type-a + b was reduced by Mn administration.
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PMID:[Studies on monoamine metabolism in the rat brain with overdosage of manganese]. 240 98

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to primates produces many of the biochemical, morphological and behavioral changes that occur in Parkinson's disease. MPTP-induced degeneration of the mesostriatal dopamine innervation has been well documented. In the present study, concentrations of dopamine and norepinephrine in cortical regions surrounding the cingulate sulcus were assessed, and were found to be markedly decreased in symptomatic MPTP-treated vervet monkeys; these results parallel the cortical involvement in Parkinson's disease. Dopamine and norepinephrine levels were not reduced in a group of asymptomatic MPTP-treated monkeys that suffered large losses of striatal dopamine concentration. If therefore appears that the dopaminergic innervations of the supplementary motor area and cingulate cortex are susceptible to MPTP-induced degeneration, but are less vulnerable than the striatal dopamine innervation.
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PMID:MPTP reduces dopamine and norepinephrine concentrations in the supplementary motor area and cingulate cortex of the primate. 240 41

Spontaneous blink rates are controlled by a definable neural system originating in PPRF with facilitatory modulation from SN and superior colliculus and inhibitory modulation provided by cerebellum and occipital cortex. The thalamus may also be involved but the result of its influence is not clear. Reflex blinking is often reduced when spontaneous blink rate is increased and the reverse applies as well. The anatomic control of reflex is primarily in structures in the caudal half of pontine tegmentum and rostral midbrain. However, SN and cerebellum and other structures that regulate blink rate also modulate reflex blinking. Neurochemical control as determined by neuropharmacological experiments is exerted by dopaminergic, cholinergic and GABAergic systems of brain stem. Dopamine activity correlates directly with blink rate whereas agonism of the other two relevant neurotransmitter systems may inhibit blink rate. Clinical implications in central nervous system disease are currently restricted to Parkinson's disease, schizophrenia and autism. In the former illness, reduced blink rate signifies a worsening of the illness and a significant increase in blink rate in patients treated with dopamine agonist may be a harbinger of agonist-induced dyskinesia. In schizophrenia, increased blink rate, even in medication-naive subjects, may signify involvement of the structures that regulate blinking. This is important because these structures are rarely invoked as sites of potential pathophysiological import in schizophrenia. Similar considerations apply to autism except that increased blinking more clearly differentiates this disorder from other forms of retardation.
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PMID:Blinking. 248 18


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