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)

Although CSF HVA is derived from brain DA metabolism the value of its determination as an index of brain DA turnover and dopaminergic activity is limited, as other factors can affect CSF concentrations. These include the partitioning of HVA between different routes of elimination from the brain, the rates of transport from CSF to blood and from the lateral ventricle to the lumbar sac, CSF space volumes, and methodologic problems. The uses and limitations of CSF HVA determination is illustrated by findings in Parkinson's disease, Huntington's chorea, motor neuron disease, disseminated sclerosis, and hepatic coma. Finally, preliminary results on the effect on CSF HVA of the DA agonist CB 154 are described.
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PMID:CSF homovanillic acid: an index of dopaminergic activity. 12 31

Huntington's chorea is a dominantly inherited disorder that usually leads to involuntary movements in the third or fourth decade. On gross pathological examination of the post-mortem brain there is a marked atrophy of the caudate nucleus and putamen. Histological examination reveals cell loss in most regions of the brain, although the hippocampus is usually remarkably free of any abnormalities. Studies to detect a biochemical defect in patients with chorea have been largely unrewarding. Since chorea appears to be the clinical counterpart of Parkinson's disease a number of investigations on dopamine metabolism have been carried out by measuring dopamine in the post-mortem choreic brain, and HVA, a metabolite of dopamine, in the CSF of patients. Most studies have found the dopamine concentrations to be normal or sometimes decreased and the activity of the biosynthetic enzyme for dopamine, tyrosine hydroxylase, is normal. The discovery that the inhibitory neurotransmitter, GABA, and the biosynthetic enzyme GAD are greatly decreased in the post-mortem choreic brain provides some rational explanation for the uncontrolled movements in this disorder. The other significant abnormality found in many, but not all, choreic post-mortem brains has been a decrease in the biosynthetic enzyme for acetylcholine, choline acetyl transferase. The evidence that GABA receptors are intact in choreic brain provides an added stimulus for the development of useful GABA-mimetic drugs. For the ultimate eradication of this distressing disorder, however, a search must continue for the primary defect in order that this can be detected before the onset of symptoms, or hopefully in amniotic fluid.
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PMID:Neurochemical findings in Huntington's chorea. 15 97

1. In the human brain, DA was found in appreciable amounts in most of the examined basal telencephalic limbic regions, with the nucleus accumbens having the highest mean level (3.38 microgram/g). In the cortical areas of the limbic lobe of Broca, DA could be measured with certainty only in the parolfactory gyrus (0.35 microgram/g). 2. In patients with Parkinson's disease, the DA concentration in the parolfactory gyrus and nucleur accumbens was markedly reduced, whereas little change was seen in the olfactory areas. Quantitatively, the DA decrease in the nucleus accumbens was of the same magnitude as in the caudate nucleus, being, in both regions, distinctly less severe than in the putamen. 3. In three cases of paranoid schizophrenia, there were no statistically significant changes of the mean levels of DA or HVA in the nucleus accumbens. However, the DA/HVA ratio was shifted noticeably in favor of HVA, possibly indicating an increase in DA turnover. This change was less pronounced in the putamen of these cases and was absent in the caudate nucleus. 4. The possibility of the substantia nigra contributing to the dopaminergic innervation of the human nucleus accumbens, as well as the significance of the observations on DA metabolism in the schizophrenic cases, is discussed.
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PMID:Dopamine in thelimbic regions of the human brain: normal and abnormal. 88 59

The effect of a new dopaminergic agonist, piribedil, was studied in 16 patients with Parkinson's disease and compared with placebo and L-DOPA. Piribedil appeared to have a moderate therapeutic effect that was significantly less than that of L-DOPA. Tremor appeared to be the main clinical feature to benefit. Nausea, vomiting, and somnolence were most frequent during the buildup of treatment and confusion and hallucinations during long-term treatment. Piribedil caused a significant decrease in probenecid-induced accumulation of HVA in the CSF, suggesting reduced turnover of endogenous dopamine in the brain. There was a significant relationship between dopamine receptor activation by piribedil and improvement of parkinsonian disability.
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PMID:Dopaminergic agonist effects on Parkinsonian clinical features and brain monamine metabolism. 109 75

The clinical management of Parkinson's disease has been revolutionized by the introduction of levodopa therapy. It has significantly reduced disability and has extended life expectancies of patients with Parkinson's disease. However, motor response fluctuations frequently appear in patients after long-term treatment with levodopa. In this study, we investigated the effect of protein-restricted diet on fluctuations in eight patients with Parkinson's disease who had been receiving long-term levodopa treatment (mean 12.5 years). Two weeks of protein-restricted daytime diet (7.5 g total at breakfast and lunch) was followed by 12.5 g total at breakfast and lunch. At night, high-protein diet (40-50 g at dinner) was offered to the patients in order to maintain total daily protein intake at Japanese standard level. The medication schedule of levodopa and other antiparkinsonian drugs was not changed within 2 weeks after the study was began. Fluctuations were reduced in 7 of the 8 patients. But in only one patient (case 6), dyskinesia and general condition got worse and stopped this therapy. Body weight, serum protein and albumin levels did not change significantly for at least three month after the study was begun in every 6 patients who were examined. Homovanillic acid level of cerebrospinal fluid reduced in every 4 patients who were examined. We concluded that protein-restricted diet during the daytime offers a fascinating technique for the control of motor response fluctuations in patients with Parkinson's disease undergoing long-term levodopa treatment. But this therapy must be indicated carefully. Mechanism of this therapy may has something to do with improvement of dopamine metabolism in the brain.
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PMID:[Influence of protein-restricted diet on motor response fluctuations in Parkinson's disease]. 130 Feb 70

The effects of GM1 ganglioside administration on functional recovery and recovery of caudate nucleus dopamine levels have been assessed in cats made parkinsonian by administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cats made severely parkinsonian by MPTP administration began to show spontaneous functional recovery by the third week after MPTP, as had been observed in previous studies with this model. In contrast, cats with similar initial impairment but which received 3 weeks of GM1 ganglioside treatment (30 mg/kg, i.p. daily) showed an accelerated behavioral recovery, showing significant functional improvement after the first week of GM1 treatment and almost normal function by the end of the third week of treatment. The GM1-treated cats had caudate nucleus dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and HVA levels significantly increased above levels measured in saline-treated MPTP control cats. A second group of cats received MPTP only until the first signs of parkinsonism were observed and thus overall had a less severe initial syndrome than the cats described previously. Again, while all cats showed functional recovery over time, the recovery process was accelerated in GM1-treated cats. GM1 treatment also caused a significant increase in caudate dopamine levels in these cats. These results suggest that GM1 ganglioside administration can result in increased dopamine levels even in the heavily denervated striatum and accelerate functional recovery after an MPTP-induced lesion of the nigrostriatal dopamine system in the cat. This suggests that GM1 or other trophic factor therapies may be fruitful treatment strategies for a disorder of nigrostriatal function such as Parkinson's disease.
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PMID:MPTP-induced parkinsonism: acceleration of biochemical and behavioral recovery by GM1 ganglioside treatment. 161 17

Behavioural and some neurochemical effects of Ro 40-7592 (3,4-dihydroxy-4'-methyl-5-nitrobenzophenone), a new COMT inhibitor, were studied in rats and mice. Ro 40-7592 increased the effect of L-DOPA (plus benserazide) on locomotor activity, reserpine-induced hypothermia, and catalepsy induced by pimozide, haloperidol and fluphenazine. Locomotor hyperactivity induced by amphetamine or nomifensine, as well as stereotypy induced by amphetamine (but not apomorphine), were also increased by Ro 40-7592. The drug stimulated exploratory activity in the open field test. It decreased the levels of HVA and 3-MT, increased the level of DOPAC but did not change the levels of dopamine in the striatum, nucleus accumbens and frontal cortex. These results indicate that Ro 40-7592 may improve the therapy with L-DOPA (plus decarboxylase inhibitor) of Parkinson's disease.
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PMID:Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a potential therapeutic activity in Parkinson's disease. 197 8

Chronic low-dose MPTP exposure was previously found to impair cognitive performance in monkeys. These monkeys developed deficits in performance of delayed response and delayed alternation tasks but maintained performance on visual pattern discrimination. This, along with other subtle behavioral changes, occurred in the absence of gross parkinsonian motor symptoms. The present study reports the results of neurochemical and neuropathological examination of the brains of these animals. Chronic low-dose MPTP exposure resulted in profound decreases in caudate dopamine (DA) levels and slightly less severe depletions in the putamen. Increases in striatal HVA/DA ratios suggest an increase in DA turnover in these areas. In contrast to striatal DA depletions, we found significant increases in striatal serotonin levels without an associated increase in serotonin turnover. At the cortical level, we found inconsistent changes in frontal cortical DA levels and variable decreases in norepinephrine levels. Since the most profound and consistent deficits were in the nigrostriatal dopamine system, we suggest that most of the behavioral consequences of chronic low-dose MPTP exposure stem from the striatal dopamine depletion. We also suggest that the maintenance of motor function in the presence of massive striatal DA depletions may be due to less impairment of putamen DA vs. caudate DA, by an increase in striatal DA turnover, a compensatory increase in serotonin availability, or a combination of these and possibly other as yet undetermined compensatory mechanisms. Furthermore, we propose the present model utilizing chronic low-dose exposure to MPTP as a model for the early, compensated form of Parkinson's disease.
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PMID:Chronic exposure to low doses of MPTP. II. Neurochemical and pathological consequences in cognitively-impaired, motor asymptomatic monkeys. 207 85

We investigated the effect of GM1 gangliosides on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Five groups of mice (saline, GM1 (30 mg/kg), MPTP, MPTP + GM1 (15 mg/kg), MPTP + GM1 (30 mg/kg] were compared. GM1 was given daily via intraperitoneal injection before and during 13 daily doses of MPTP (30 mg/kg). Mice were tested for locomotion (1) within 2 h of an MPTP dose (to measure reduced motor activity), and (2) within 24 h of an MPTP dose (after animals had recovered and exhibited hyperactivity). We found that mice given GM1 gangliosides exhibited significantly less MPTP-induced behavior. This effect was most evident with the 15 mg/kg GM1 dose. GM1 also appeared to attenuate MPTP-induced neurochemical changes. GM1 effects indicating enhancement of DA turnover and preservation of DA, DOPAC and HVA concentrations in the striatum were found after the 8th MPTP dose. These latter neurochemical changes, however, were transient and not present after the 13th MPTP dose. Our data would suggest that gangliosides may reduce acute MPTP-induced neurotoxicity in mice either through an increase in DA neuron survival and/or the augmentation of striatal DA activity.
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PMID:GM1 gangliosides alter acute MPTP-induced behavioral and neurochemical toxicity in mice. 225 Jan 72

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


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