Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various doses (0.1-0.5 mg/kg i.p.) of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, produced a dose-dependent increase in well-coordinated locomotor activity of NMRI mice. Higher doses (greater than 0.5 mg/kg) produced a typical motor syndrome characterized by head weaving, body rolling, ataxia and salivation. MK-801, 0.2 mg/kg i.p., a dose which produced marked locomotor stimulation, increased the rate of disappearance of dopamine in the striatum and in the limbic forebrain of the animals, whereas the rate of disappearance of noradrenaline remained unchanged in the limbic forebrain and in the hippocampus. MK-801 increased the rate of tyrosine hydroxylation (measured as the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of DOPA decarboxylase) in the striatum with no change in DOPA formation in the limbic forebrain. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) remained unchanged both in the striatum and in the limbic forebrain following the administration of MK-801. It is concluded that MK-801 may facilitate the activation of dopaminergic mechanisms through an indirect (perhaps by reducing glutamatergic activity) rather than a direct effect on dopamine neurons.
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PMID:Effect of the NMDA receptor antagonist, MK-801, on locomotor activity and on the metabolism of dopamine in various brain areas of mice. 182 83

Long-Evans dams were fed either a vitamin B6-deficient or a control diet from day 13-14 of gestation and throughout lactation. A control pair-fed group was also included because of differences in food intake between vitamin B6-deficient and control ad libitum dams. The progeny of vitamin B6-deficient dams had all the classic symptoms of B6 deficiency. These included weight loss, ataxia, tremor, and epileptic seizures. Concentrations of the neurotransmitter dopamine (DA), and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as D-2 dopamine receptor binding, 3,4-dihydroxyphenylalanine (DOPA) decarboxylase activity, and vitamin B6 levels were measured in the corpus striatum of progeny at 7, 14, and 18 days after birth. Striatal DA and HVA levels were significantly decreased in B6-deficient animals when compared to ad libitum or pair-fed controls. Daily injections of vitamin B6 to deprived animals from the 14th to 18th day after birth improved the abnormal movement and normalized the concentration of DA but not of HVA in corpus striatum. Striatal D-2 dopamine receptor binding using [3H]spiperone as ligand was significantly reduced in 18-day-old animals as compared to ad libitum and pair-fed controls. No significant differences were found at 14 days. The administration of vitamin B6 to deprived animals did not raise the level of D-2 receptor binding during the period of observation. Scatchard plots indicated that the differences in binding were due to changes in receptor number and not in KD. Corpus striatum DOPA decarboxylase activity with and without the addition of exogenous pyridoxal phosphate was significantly reduced in 14- and 18-day-old animals when compared to pair-fed controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of perinatal vitamin B6 deficiency on dopaminergic neurochemistry. 379 15

We report on two sisters with a childhood-onset form of predominantly axial dystonia with marked diurnal fluctuations. Onset of clinical features was at approximately 6 years of age. Associated features included marked fatigue, slight facial dysmorphism, short stature, obesity, and learning disability*. Dystonia and fatigue responded to 3,4-dihydroxyphenylalanine (DOPA) therapy, with recurrence of symptoms upon withdrawal; the efficacy has been maintained over 7 years. Other symptoms were not influenced. There was no other case in the family (which included an older, healthy brother), except for non-specific fatigue without dystonia in the mother, and there was no significant family history except for obesity on the father's side. These observations are discussed in relation to the classical descriptions of Segawa syndrome, and to more recent reports of childhood onset, age-related, and transient benign paroxysmal tonic upgaze and ataxia. The combination of symptoms, their sensitivity to DOPA, and their persistence throughout childhood constitute, to our knowledge, a new clinical entity, which we propose to categorize as a DOPA-sensitive dystonia-plus syndrome.
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PMID:DOPA-sensitive dystonia-plus syndrome. 1573 26