Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thallium, a rodenticide, has been shown to produce several neurological symptoms including motor weakness, ataxia, tremor, convulsion, coma and death. The present study was designed to evaluate the effects of acute or subacute exposure to thallium on several neurochemical biomarkers in rat brain. In the acute study, adult male CD rats were treated with 0 or 20 mg thallium/kg intraperitoneally (ip) and sacrificed 2, 6, or 24 hr after exposure. In the subacute study, animals were treated with 0 or 5 mg thallium/kg ip daily for 10 days and sacrificed 24 hr after the last dose. Acute injections of thallium produced in the frontal cortex significant increases in glutamine concentration after 6 hr and in taurine after 6 and 24 hr. In hippocampus, significant decreases in aspartic acid and taurine concentrations were found after 6 hr. Subacute exposure to thallium produced significant increases of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and serotonin (5-HT) in amygdala and increases in 5-HT concentration in hypothalamus. DA or muscarinic cholinergic (MCh) receptor binding did not show any significant alterations in caudate nucleus or frontal cortex after acute or subacute exposure to thallium. However, when membranes prepared from control caudate nuclei were incubated with thallium (1-100 microM) in vitro, we observed a dose-dependent decrease in DA and MCh receptor binding. These data suggest that the neurotoxicity produced by thallium exposure may be associated with changes in the concentrations of amino acids and other neurotransmitters in various regions of the rat brain.
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PMID:Thallium intoxication produces neurochemical alterations in rat brain. 217 76

1. The metabolism of mouse thioglycollate-elicited peritoneal macrophages was studied in culture for up to 96 h. 2. The rates of glycolysis, lactate formation and glutamine utilization were approximately linear with time for at least 80 h of culture. 3. The rates of glucose and glutamine utilization by cultured macrophages were approx. 500 and 90 nmol/h per mg of protein respectively. This rate of glucose utilization is at least 50% greater than that previously reported for macrophages during 60 min incubation in a shaking flask; and it is now increased by addition of glutamine to the culture medium. The rate of glutamine utilization in culture is similar to that previously reported for macrophages during 60 min incubation. The major end-product of glucose metabolism is lactate, and those of glutamine metabolism are CO2, glutamate, ammonia and alanine. 4. Oleate was utilized by these cells: 14C from [14C]oleate was incorporated into CO2 and cellular lipid. The highest rate of oleate utilization was observed when both glucose and glutamine were present in the culture medium. The presence of oleate in the culture medium did not affect the rates of utilization of either glucose or glutamine. Of the [14C]oleate incorporated into lipid, approx. 80% was incorporated into triacylglycerol and only 18% into phospholipid. 5. The turnover rate for the total ATP content of the macrophage in culture is about 10 times per minute: the value for the perfused isolated maximally working rat heart is 22. This indicates a high metabolic rate for macrophages, and consequently emphasizes the importance of the provision of fuels for their function in an immune response.
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PMID:Rates of utilization of glucose, glutamine and oleate and formation of end-products by mouse peritoneal macrophages in culture. 277 7

Male, Fischer strain 344 adult rats were given various doses (25-100 mg/kg) of p,p'-DDT by oral gavage, and levels of biogenic amines, their metabolites, and amino acid neurotransmitters, tremor activity, and rectal temperature were measured at several intervals (2, 5, 12, and 24 h) after dosing. Dose-related increases in rectal temperature and in tremor activity were observed at 50-100 mg/kg 12 h after dosing. Tremorigenic doses of DDT increased the 5-hydroxyindoleacetic acid (5-HIAA) level in hypothalamus, brainstem, and striatum, whereas doses of 75 and 100 mg/kg increased the 3-methoxy-4-hydroxyphenylglycol (MHPG) level in hypothalamus and brainstem and the 3,4-dihydroxyphenylacetic acid level in striatum. Six amino acids were assayed in the brainstem, hypothalamus, and striatum; aspartate and glutamate levels were increased only in brainstem at 25-100 mg/kg. No consistent changes in concentrations of taurine, glutamine, glycine, or gamma-aminobutyric acid were observed in any of the regions assayed. Time-related increases in rectal temperature were seen 2-12 h after dosing, and the presence of tremor was observed 5-12 h after dosing; for both the time of peak effect was at 12 h. The DDT-induced hyperthermia and tremor were associated with dose- and time-related increases in levels of 5-HIAA, MHPG, aspartate, and glutamate. It is suggested that an increase in the turnover rate of 5-hydroxytryptamine (5-HT) may be responsible for the DDT-induced hyperthermia, whereas increases in the metabolism of 5-HT and norepinephrine may be involved in the tremor.
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PMID:Effects of p,p'-DDT on the rat brain concentrations of biogenic amine and amino acid neurotransmitters and their association with p,p'-DDT-induced tremor and hyperthermia. 286 92

Oral administration of 120 or 240 mg/kg permethrin produced dose- and time-related tremor in rats with the peak effect occurring 5 hrs after dosing. Subsequent experiments done 5 hrs postdosing found that 45 to 180 mg/kg permethrin produced dose-related increases in rectal temperature and enhanced responsiveness to an acoustic stimulus. Tremor was detected at 90 and 180 mg/kg. Neurochemical analyses of regional biogenic amines and their metabolites and amino acids 5 hrs after 90 or 180 mg/kg indicated that 5-HIAA levels were increased in the hypothalamus (HYP), brain stem (BS), hippocampus (HPC), and striatum (STR); 5-HT was not affected. MHPG was increased in the HYP and BS, while NE was decreased at the high dose only. DOPAC and HVA were increased in the STR after 90 and 180 mg/kg, while DA was not affected. Aspartate levels were increased in the BS and STR; glutamate was increased in the BS. Taurine, glutamine, glycine, and GABA were not affected. A time-course analysis of neurochemical changes 2, 5, 12, and 24 hrs postdosing indicated that 5 hrs was the time of peak effect for permethrin. Permethrin-induced tremor and hyperthermia were significantly correlated with dose- and time-related changes in MHPG, 5-HIAA, and ASP.
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PMID:Neurobehavioral effects of permethrin are associated with alterations in regional levels of biogenic amine metabolites and amino acid neurotransmitters. 287 38

Regional amino acid concentrations were measured in rat brain fixed by microwave irradiation at three levels of elevated atmospheric pressure corresponding to different phases of the high-pressure neurological syndrome [20 atmospheres absolute (ATA), no clinical signs; 60 ATA, tremor; 85 ATA, severe tremor and myoclonic jerks]. No changes in amino acid content occurred at 20 or 60 ATA. At 85 ATA glutamine content increased in hippocampus, striatum, cerebellum, and substantia nigra, and gamma-aminobutyric acid content increased in hippocampus. It is suggested that enhanced glutamate release in various subcortical structures contributes to the myoclonic activity observed at 85 ATA.
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PMID:Regional amino acid concentration in the brains of rats exposed to high pressures. 371 8

Five vervet monkeys were administered increasing doses (4--12 mg/kg/day) of d-amphetamine over a period of 35 days. Three phases od behavioural change were discerned: phase 1 during which animals exhibited repetitive stereotyped action sequences with rapid head movements, occasional abnormal grooming, picking at the cage, hand-staring and snatching; phase 2 in which behaviour became progressively more restricted and animals became markedly unresponsive to auditory, visual and tactile stimuli; phase 3 was characterised by the abrupt development of gross over-responsiveness to environmental stimuli, ataxia and tremor. At post-mortem, by comparison with controls, amphetamine-treated monkeys showed marked depletions of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in corpus striatum and cerebral cortex and reductions in the activities of tyrosine hydroxylase and dopa decarboxylase in striatum. Turnover of these monoamines, assessed by high-performance liquid chromatography determinations of their respective metabolites, was also reduced. These findings are interpreted as evidence of monoamine neurone destruction, most severely in the case of DA neurones. Though there was a non-significant reduction in 3H-spiperone binding (reaching almost 50% in nucleus accumbens), numbers of receptors for the monoamines nA and 5-HT were not significantly changed, and the activities of the enzymes choline acetyltransferase and glutamine decarboxylase were similar in experimental and control animals. The contrast of these findings with those seen in post-mortem brains in schizophrenia is discussed.
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PMID:Behavioural and biochemical effects of chronic amphetamine treatment in the vervet monkey. 613 May 56

Paralytic tremor (pt) is a sex-linked mutation in rabbit that affects myelination of the CNS. Myelin in the pt brains represents approximately 30% of the normal levels. Previously we showed that the pt mutation affects primarily proteolipid protein (Plp) gene expression. In the present study we investigated the relative effect of the pt mutation on two distinctive Plp gene products, PLP- and DM-20-specific messenger RNAs. Our results showed that both PLP and DM-20 are affected and that the ratio DM-20/PLP was higher in pt rabbits than in age-matched controls. We sequenced normal rabbit PLP cDNA and characterized pt mutation at the DNA level. Rabbit PLP sequence, deduced from cDNA, differs from the human protein only at Thr198. Sequence analysis of the mutant cDNA revealed a transversion T-->A in exon 2 of the Plp gene. This point mutation, which is placed at the end of the first potential transmembrane domain, results in a substitution of His36 by a glutamine. This transversion abolishes a restriction site that enabled us to screen a large number of animals and observe a perfect correlation between the pt allele and the abnormal phenotype.
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PMID:Paralytic tremor (pt): a new allele of the proteolipid protein gene in rabbits. 752 75

Proteolipid protein (PLP) is a major myelin protein of the central nervous system. Mutations of the Plp gene are responsible for a number of sex-linked disorders in humans (Pelizaeus-Merzbacher disease) and in animals. We have identified a novel mutation of the Plp gene which gives rise to the paralytic tremor (pt) phenotype in rabbit. Pt rabbits are hypomyelinated and present very low levels of PLP protein and its mRNA. Sequence analysis revealed a single nucleotide change in exon 2 which results in the substitution of a histidine by a glutamine at position 36. Histidine36 is positioned at the boundary of the first transmembrane domain. Therefore, its position can be crucial for the efficient interaction of PLP with other proteins and lipids, and for correct incorporation into the membrane.
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PMID:Myelin proteolipid protein mutation in the rabbit: a new model of Pelizaeus-Merzbacher disease. 753 32

Determinations of biopterin (BP), homovanilic acid (HVA), glutamic acid (GTA), and glutamine (GT) levels in cerebrospinal fluid (CSF) obtained through a lumbar tap were performed in 20 parkinsonian patients in different stages of evolution and without medication. In patients with motor symptoms not related to Parkinson's disease (dystonia, dyskinesia and essential tremor) (n = 4). In 7 other neurological patients subjected to spinal tap for diagnostic procedures neurotransmitters were also determined and taken as control groups. In 14 of the patients with Parkinson's disease, the symptoms were evaluated using conventional scales (UPDS, NYPDS, NWPDS, Schwab and England, and Hoehn and Yahr scale). The amplitude and the frequency of tremor were quantitatively evaluated through a single plane accelerometer Grass SP-1, akinesia was measured through reaction time to auditory stimuli, and rigidity through the speed of lineal movement. Evaluations were performed with the patient not on any medication for 1 week and repeated 1 h after the intake of 250 mg of 200/50 L-dopa/carbidopa preparation (Sinemet) and on a different day after the intake of biperiden (Akineton) 6 mg/day. Differences in neurotransmitter or metabolites levels between Parkinson's disease and control groups were determined through an independent Student's t test. Correlation between severity of symptoms in the scales and for each individual symptom measured through the quantitative tests and the levels of neurotransmitters in CSF were evaluated through the Pearson correlation analysis test. Modifications in the motor performance after administration of Sinemet and Akineton, and the levels of neurotransmitters were indirectly determined. RESULTS. (1) There were significant differences between the levels of BP and GT in patients with Parkinson's disease and control groups, (2) lower GTA levels correlated with more severe rigidity and akinesia, and with the best response to the administration of L-dopa and may be an important marker for prognosis, and (3) lower levels of GT correlated with least akinesia, but not with tremor, which may indicate that the akinesia depends on other biochemical abnormalities besides dopamine depletion.
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PMID:Neurotransmitter levels in cerebrospinal fluid in relation to severity of symptoms and response to medical therapy in Parkinson's disease. 763 Oct 94

Myelin/oligodendrocyte glycoprotein (MOG) is a minor myelin protein that belongs to the immunoglobulin gene superfamily and evokes demyelination based on immunological response. Localized preferentially at the external surfaces of myelin sheaths, it is one of the primarily target autoantigens in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Elevated MOG content has been found in the myelin fraction of the rabbits affected by the mild form of paralytic tremor (pt) disease, evoked by natural, point mutation in exon 2 of plp gene. A single T-->A transversion results in substitution of histidine36 by glutamine in PLP and it's splicing variant DM-20 molecules. The affected animals, although strictly controlled for pt trait, differ significantly in their phenotypes, distinguished by the severity of neurological symptoms. It was shown that the degree of CNS hypomyelination and deficiency of PLP/DM-20 correlates well with the severity of neurological symptoms and is highest in the most strongly affected animals. Variety of phenotypes generated from pt genotype together with previously observed MOG hyperexpression suggested possible contribution of immunological component to the pt disease. Present studies indicate that MOG expression depends both on the phenotype and the age of affected rabbits and most probably mirrors retardation in myelinogenesis process caused by pt mutation.
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PMID:pt point mutation in plp gene results in hyperexpression of MOG in hypomyelinated rabbit. 878 15


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