Reversible inactivation of rat brain pyruvate dehydrogenase multienzyme complex by pyridoxal 5'-phosphate.
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Animals↗
Biomedical subjects
A Barbeau
Publications and source records attributed to A Barbeau.
Effect of brain peptides on hypokinesia produced by anterolateral hypothalamic 6-OHDA lesions in rats.
Intraventricular injections of substance P, TRH and somatostatin were administered to rats rendered hypokinetic by bilateral microinjections of 6-hydroxydopamine into the anterolateral hypothalamus, Only substance P in a dose of 0.30 micrigrams/rat significantly increased motor activity as determined by photocell counts in a 5 min test session immediately after administration of the peptide. Behavioral observations indicated that grooming and not locomotion was mainly responsible for the greater activity scores. None of the three peptides at the doses examined potentiated or reduced the increased activity induced by 1 mg/kg apomorphine. Stereotyped behavior was also not affected by previous injections of substance P and somatostatin but was enhanced in animals which had received 5 micrograms/rat TRH 30 min prior to apomorphine.
Animals↗
Methylmercury poisoning in Canadian Indians--the elusive diagnosis.
A World Health Organization Expert Committee has concluded that symptoms of methylmercury poisoning may appear at blood concentrations of 200-500 ng Hg/ml. Blood levels in this range have been found in several Indian and Inuit communities in Canada. The syndrome of severe methylmercury poisoning (Hunter-Russell syndrome) is well described. However, diagnosis of less severe cases is difficult. This paper review the present situation in Canada. The problems of diagnosis currently being encountered are discussed and are illustrated by the case of an individual who had one of the highest blood concentrations (551 ng Hg/ml) ever described in fish-eating populations outside of the outbreaks in Minamata and Niigata in Japan. Although mercury concentrations in brain were estimated to have been in the "symptomatic" range at least once in the two years prior to his death, neurohistological examination was normal. Detailed examination by two teams of neurologists revealed effects that may be associated with methylmercury poisoning but a definitive diagnosis remained elusive.
Aged↗
Electromyography and nerve conduction studies in Friedreich's ataxia and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
Twenty four ataxic patients were investigated with electromyography and nerve conduction studies. They were divided in two groups according to the area they came from, the evolution of the disease, and the clinical signs. Group I patients from the Rimouski area displayed all the clinical and electrophysiological signs of Friedreich's ataxia. Group II comprised patients who presented with a new syndrome known as the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Although the clinical evolution was better in the latter, there were more electromyographic signs of denervation and the motor conduction velocities were slower. Both groups showed identical and important abnormalities in sensory nerve conduction. The results of electrophysiological studies in spastic ataxia have not been reported to our knowledge. They underline the place of spastic ataxia as distinct from Friedreich's ataxia, spastic paraplegia, and the known familial neuropathies.
Action Potentials↗
Electroencephalographic findings in Friedreich's ataxia and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
Electroencephalographic studies have been done in two groups of hereditary ataxia: a group bearing the classical features of Friedreich's ataxia and a group clinically different described as autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The qualitative anomalies observed in the two groups were similar and were comparable with the data reported in the literature. However, the main difference between the two groups is the greater incidence of EEG abnormalities in the ARSACS group, which suggests more involvement of the cortical and subcortical structures. This is reinforced by the lower I.Q. performance in the latter patients. Some comments are made about focal EEG findings, behavior and I.Q. In general, EEG was not considered a valuable instrument for diagnosis since no qualitative electric pattern could be identified. With regard to prognosis, EEG cannot be used as a criterion, since there is no relation between the degree of anomalies and the severity of the disease and since EEG does not worsen with the progression of the disease.
Adolescent↗
The neuropathy of Charlevoix-Saguenay ataxia: an electrophysiological and pathological study.
Two female patients aged 30 and 40 years with the Charlevoix-Saguenay ataxia were studied. Both had absent sensory action potentials in upper and lower extremities but, unlike typical cases of Friedreich's ataxia, they displayed a marked slowing of motor conduction velocities. Sural nerve biopsies taken from calf and ankle revealed a severe loss of large myelinated axons contrasting with a normal myelinated fiber density. Evidence for active axonal degeneration was scarce, with no indication of axonal regeneration. Teased myelinated fibers revealed an increased variability of internodal length but no evidence for myelin breakdown. These findings support, as a primary defect, a developmental abnormality of peripheral nerve, namely a lack of maturation of large myelinated axons and possibly a faulty myelination of nerve fibers. We think it is unlikely to represent a progressive axonal atrophic or dystrophic process, as suggested in Friedreich's ataxia.
Action Potentials↗
A cluster of Friedreich's ataxia in Rimouski, Québec.
We described a cluster of 8 independent sibships of Friedreich's ataxia in the St-Fabien parish of Rimouski and have shown that they are all related within 6 generations. The study of this geographic and genetic isolate permitted the investigation of certain unusual features of the disease such as constant myopia, delayed reaction times to pain, flexor spasms, and a rapid evolution.
Adolescent↗
Measurement of ataxia and related neurological signs in the laboratory rat.
The purpose of the present study was to design a standard battery of tests capable of quantitatively characterizing ataxia and concomitant neurological signs in the rat. In addition to a systematic analysis of the walking gait of animals, tests for activity, catalepsy, rigidity, and various reflexive responses were included in the battery. The standardization and validation of the test system was performed by determining and comparing profiles of neurobehavioral effects produced by 3-acetyl pyridine, acrylamide, pyrithiamine, and thiamine deficiency, four experimental treatments reported to induce ataxia in animals. Results indicate that profiles of neurobehavioral disturbances accompanying ataxia in animals varied distinctively with each experimental treatment.
Acrylamides↗
Amino acid changes in thiamine-deficient encephalopathy: some implications for the pathogenesis of Friedreich's ataxia.
Thiamine-deficient encephalopathy in the rat is characterized by ataxic gait, loss of righting reflex and curvature of the spine. Neurochemical changes include a diminished activity of cerebral pyruvate decarboxylase leading to abnormal pyruvate oxidation. The present study shows that this defective pyruvate oxidation produces a significant depletion of three important amino acid neurotransmitters, namely gamma aminobutyric acid (GABA), glutamic acid, and aspartic acid. Such changes could lead to severe neuronal dysfunction and the observed neurological symptoms of thiamine deficiency. Some implications for the pathogenesis of Friedreich's ataxia are discussed.
Amino Acids↗
The Syrian golden hamster: a model for the cardiomyopathy of Friedreich's ataxia.
In light of the available information on the cardiomyopathy of Friedreich's ataxia, the cardiomyopathic Syrian hamster may be an appropriate laboratory model. Cardiomyopathy in these animals is a result of calcium accumulation. We analyzed the atria and right and left ventricles from cardiomyopathic (CM) and random bred (RB) animals for calcium, magnesium, and iron concentrations at 30-40 and 60-70 days of age (age of maximum lesioning). There are no significant differences in the concentration of iron or magnesium among age-matched groups. The concentration of calcium in the left ventricles of the CM animals at 60 days old is 14 fold higher than that of RB animals. Although there is a significant difference in the concentration of calcium in the left ventricles of younger animals, it is not as pronounced as the difference in older animals. Analysis of the taurine concentration in 30-40 day old animals revealed that the CM animals show slightly higher taurine concentrations than RB in the whole heart. In 60 day old CM hamsters in the beta-adrenergic receptor density of the ventricles is unchanged. This indicates that calcium overload is not due to adrenergic supersensitivity.
Animals↗
Erythrocyte protoporphyrin levels in patients with Friedreich's and other ataxias.
Of 13 patients with Friedreich's ataxia (Type Ia) and 17 with type IIa recessive ataxias, all were found to have levels of "free erythrocyte protoporphyrin" (FEP) above the normal range. The rise in FEP in Friedreich's ataxia correlated well with the age of the individual and thus appears to be related to the course of the disease. Subjects with olivo-ponto-cerebellar atrophy, Charlevoix syndrome, Duchenne muscular dystrophy, and Parkinson's disease were also found to have significantly elevated FEP, although the distribution overlapped with the normal range. The finding of elevated FEP may indicate a relative heme deficiency in ataxia due to inhibition of ferrochelatase leading to a state of ineffective, persistent erythropoiesis. The possibility of a prostaglandin abnormality being related to this defect and to the pathogenesis of ataxia is considered.
Adolescent↗
Regional distribution of amino acids in Friedreich's ataxia brains.
The distribution of amino acids in two Friedreich's ataxia brains is compared to 4 control brains. Glutamate and GABA were decreased in the cerebellar hemispheres and/or in the vermis. Taurine concentrations were uniformly elevated throughout the areas studied. Taurine/glutamate and taurine/GABA ratios were consistently elevated in Friedreich's ataxia brains, whereas glutamate/glutamine ratios were consistently decreased (with normal glutamine concentrations).
Amino Acids↗
Brain neurotransmitter receptors in Friedreich's ataxia.
The binding of 3H-quinuclidinyl benzilate, a muscarinic cholinergic antagonist, of 3H-dihydroalprenolol, a beta adrenergic antagonist, and of 3H-flunitrazepam, a ligand which labels benzodiazepine receptors, was examined in several regions of control and Friedreich's ataxia (FA) brains. 3H-Quinuclidinyl benzilate binding appeared to increase in the inferior olivory nucleus, anterior and posterior cerebellar vermi but was unaltered in the dentate nucleus and cerebellar hemisphere of FA brain. The binding of 3H-dihydroalprenolol seemed to increase in the inferior olivary nucleus yet was not different from controls in the dentate nucleus, cerebellar hemisphere, anterior and posterior cerebellar vermi of FA brains. 3H-Flunitrazepam binding was slightly lowered in the inferior olivary and dentate nuclei but was unchanged in the other FA brain regions examined. The present study suggests possible trends in neurotransmitter receptor alterations in post-mortem brain tissue of FA patients.
Adult↗
Dicarboxylic amino acid uptake in normal, Friedreich's ataxia, and dicarboxylic aminoaciduria fibroblasts.
Glutamic and aspartic acid uptake was measured in skin fibroblasts from patients with Friedreich's Ataxia, dicarboxylic aminoaciduria, and normal individuals. The results showed no difference in uptake kinetics of either dicarboxylic amino acids between Friedreich's Ataxia and normal cells, but reduced uptake velocities in dicarboxylic aminoaciduria fibroblasts. Friedreich's Ataxia fibroblasts were, however, less calcium-dependent and more magnesium and phosphate-dependent than controls in glucose-free incubation mixture. This difference might be related to some degree of glucose intolerance by Friedreich's Ataxia fibroblasts in culture.
Amino Acids↗
Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich's ataxia-demonstration of a low linoleic acid content most evident in the cholesterol-ester fraction.
Studies were undertaken to further characterize plasma lipids and lipoprotein abnormalities in Friedreich's ataxia. The high density lipoprotein (HDL) apo AI/AII ratio was quantitated by densitometry and found to be normal. The free to esterified cholesterol ratio in HDL was lower in Friedreich's ataxia because of a reduction in the amount of free cholesterol in this lipoprotein class. The fatty acid profile of the cholesteryl-ester (CE) fraction was markedly deficient in linoleic acid (18:2) in both total plasma and HDL. There was a compensatory increase in saturated acids. The HDL phospholipid (PL) fraction also showed a reduction in the proportion of 18:2 with a concomitant increase in stearic (18:0) and oleic acid (18:1) while the HDL triglyceride (TG) fraction showed only an increase in palmitoleic (16:1) and oleic acids. Feeding of soya lecithin rich in 18:2 failed to increase significantly the 18:2 content of HDL-CE and HDL-PL but lowered the percentage of 16:1 and 18:1 in all 3 lipid classes of HDL. Although the total plasma CE fatty acid profile was perturbed in Friedreich's Ataxia, total plasma PL and TG fatty acid patterns were unaffected. Among the plasma lipoprotein fatty acid profiles, that of the low density lipoprotein (LDL) was most affected, then that of the HDL. The very low density lipoprotein (VLDL) fatty acid composition showed an increase in 16:1 and a decrease in 18:2 which were entirely corrected by lecithin feeding. These results suggest the existence of a metabolic defect in the incorporation of 18:2 into chylomicron phospholipids within the intestinal mucosa.
Adolescent↗
Pilot studies on membranes and some transport mechanisms in Friedreich's ataxia.
The observed anomalies in high density lipoproteins in Friedreich's ataxia led us to investigate the state of cellular membranes in this illness. As a preliminary screening program, we studied the shape of erythrocytes; the phospholipid content of platelets and the transport properties of these membranes as indirectly reflected in the absorption of Vit E and the renal handling of orally injected taurine. All these investigations were normal, except for a tendency towards more echinocytes in Friedreich's ataxia and the insignificant increase in taurine urinary excretion after an oral load. We concluded that the possible membrane abnormalities are not major and will have to be searched for with more subtle and specific tests.
Adult↗
Erythrocyte membrane lipids in Friedreich's ataxia.
In a study of the lipid composition of erythrocyte membranes in Friedreich's ataxia, the concentration of the major membrane components (phospholipids, cholesterol and protein) in ataxic patients, family members, and control subjects were found to be the same. The total fatty acid distribution was also normal. However, an altered distribution of phospholipid classes in erythrocytes was noted (an increase of PI + PS and a decrease of PE in Friedreich's ataxia patients).
Adult↗
Evidence for an altered physical state of membrane proteins in erythrocytes in Friedreich's ataxia.
Electron spin resonance, scanning electron microscopic, and SDS-polyacrylamide gel electrophoretic studies of erythrocytes in Friedreich's ataxia have been performed. No alteration in the physical state of membrane lipids, in morphology, or in the staining profile of erythrocytes in Friedreich's ataxia could be demonstrated. An altered conformation and/or organization of proteins in erythrocyte membranes in this disorder was suggested by spin labeling studies (P less than 0.025), favoring the possibility of a generalized membrane abnormality in Friedreich's ataxia. These findings are discussed in relation to other inherited neurological diseases where similar studies have been performed.
Electron Spin Resonance Spectroscopy↗