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Biomedical subjects

O Hornykiewicz

Publications and source records attributed to O Hornykiewicz.

At least 73 records · Page 4Linked to original sources
PubMed1988

Dementia, parkinsonism, and motor neuron disease: neurochemical and neuropathological correlates.

The neurochemical markers for the major neurotransmitter systems were measured in the brain of a patient who died with a dementia-parkinsonism-motor neuron disease (DPMN) syndrome complex. Moderate neuronal loss in the substantia nigra, spongiform changes in the frontal cortex, and moderate anterior horn cell loss throughout the spinal cord were observed. A severe nigrostriatal dopamine deficiency provides the basis for the observed parkinsonian features. The dementia is unexplained.

Caudate Nucleus↗
PubMed1987

The dopamine autoreceptor agonist B-HT 920 inhibits in vivo dopamine release into the cerebroventricular system of cats.

In anesthetized cats the dopamine autoreceptor agonist B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine), 1 mg/kg i.v., greatly decreased the amount of dopamine in cerebroventricular perfusates. This effect was antagonized by a low dose (50 micrograms/kg i.v.) of haloperidol, but not by the alpha 2-adrenoceptor blocker idazoxan. Our observations provide evidence that B-HT 920 inhibits brain dopamine release in vivo and may be therapeutically valuable in diseases presumed to be accompanied by a predominance of brain dopamine activity, such as Huntington's disease, mania and schizophrenia.

Adrenergic alpha-Agonists↗
PubMed1987

Elevated serotonin and reduced dopamine in subregionally divided Huntington's disease striatum.

We measured the rostrocaudal distribution of serotonin, dopamine, and their metabolites in Huntington's disease striatum (caudate and putamen). Mean levels of serotonin or 5-hydroxyindoleacetic acid were elevated in most striatal subdivisions, whereas concentrations of dopamine or its metabolite homovanillic acid were slightly to markedly reduced. Dopamine and serotonin were at control levels in the nucleus accumbens and substantia nigra. Whereas the above-normal serotonin can most likely be accounted for by striatal atrophy, the reduced dopamine suggests either a marked down-regulation of nigrostriatal dopamine neurons or an actual reduction in the arborization of the striatal dopamine neurons. As experimental animal data suggest, the relative excess of striatal serotonin or one of its metabolites may facilitate the neurodegenerative process in Huntington's disease striatum.

Brain↗
PubMed1987

Effect of mannitol treatment on brain neurotransmitter markers in kainic acid-induced epilepsy.

The effect of mannitol treatment on the behavioural, morphological and neurochemical brain damage induced after subcutaneously applied kainic acid (10 mg/kg) was studied in the rat. Mannitol at a dose of 1.5 g/kg was injected intravenously 10 min, 1.5 h and 3 h respectively after kainic acid administration. A protective effect of mannitol was observed only when mannitol was given 1.5 h after kainic acid application, i.e. within the early phase of kainic acid-induced brain oedema development. At this time period, mannitol prevented the development of kainic acid-induced seizures as well as irreversible brain lesions and neurochemical changes, the latter being reduction of noradrenaline levels in amygdala/pyriform cortex measured 3 h, and reduction of glutamate decarboxylase and choline acetyltransferase activities measured 3 days after kainic acid treatment. Similarly loss of glutamate decarboxylase activity in dorsal hippocampus induced by kainic acid was prevented by mannitol treatment. It is concluded that by washing out brain oedema, mannitol treatment may prevent propagation of seizures and brain damage in the kainic acid model of epilepsy.

Animals↗
PubMed1986

The dopamine autoreceptor agonist B-HT 920 stimulates denervated postsynaptic brain dopamine receptors in rodent and primate models of Parkinson's disease: a novel approach to treatment.

B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]azepine), an agonist at alpha 2-adrenoceptors and at dopamine autoreceptors, was tested with respect to stimulation of postsynaptic brain dopamine receptors in mice, rats and rhesus monkeys. In mice B-HT 920 (0.2-20 mg/kg s.c.) injected 4 h after reserpine did not stimulate locomotor activity; this was in contrast to apomorphine (0.1-10 mg/kg s.c.) which elicited locomotor activity in a dose-dependent manner. However, B-HT 920 was effective in inducing locomotor activity when injected 12, 24 and 48 h after reserpine. This effect was dose-dependent and increased with the duration of reserpine pretreatment. In naive rats, B-HT 920 (0.02-2.0 mg/kg s.c.) only decreased exploratory activity and did not elicit stereotyped activity in doses up to 4 mg/kg s.c. This was in contrast to the stereotypy-inducing effect of apomorphine (2.0 and 4.0 mg/kg s.c.). In rats with unilateral striatal ibotenic acid lesion, B-HT 920 (0.2-2.0 mg/kg s.c.) was ineffective in producing significant ipsilateral rotation, whereas apomorphine (0.5-10.0 mg/kg s.c.) was very potent in this model. In rats with unilateral 6-OH-dopamine lesions of the medial forebrain bundle B-HT 920 elicited strong contralateral rotation in a dose-dependent manner (0.02-1.0 mg/kg s.c.). In this model B-HT 920 was equi-effective but long acting when compared with apomorphine. The contralateral rotation produced by B-HT 920 was antagonized by the D2-antagonist sulpiride but not by the D1-antagonist SCH 23390. In rhesus monkeys with severe parkinson-like symptoms induced by MPTP, B-HT 920 in doses of 10 micrograms/kg i.m. and higher restored normal behavior, resulting in complete relief of parkinson symptoms in all animals with 100 micrograms/kg i.m. It is concluded that the property of B-HT 920 to stimulate the 'denervated' supersensitive (reserpine, 6-OH-dopamine, MPTP) but not the normosensitive postsynaptic dopamine receptor in the striatum may represent a novel principle for a specific approach to dopamine substitution treatment of Parkinson's disease.

Animals↗
PubMed1986

Brain neurotransmitters in dystonia musculorum deformans.

We examined histologically and biochemically the brains of two patients with generalized childhood-onset dystonia musculorum deformans. We found no important histologic changes in the basal ganglia, cerebral cortex, higher brain-stem nuclei, locus ceruleus, or raphe nuclei. Similarly, the activity of choline acetyltransferase and the levels of gamma-aminobutyric acid and glutamic acid in the cerebral cortex and basal ganglia were within the control range. In contrast, the norepinephrine concentrations were markedly and consistently decreased in the lateral and posterior hypothalamus, mamillary body, subthalamic nucleus, and locus ceruleus. The serotonin level was subnormal in the dorsal raphe nucleus, as was the dopamine level in the nucleus accumbens and, in one of the two cases, in the striatum. Elevated concentrations of norepinephrine were found in the septum, thalamus, colliculi, red nucleus, and dorsal raphe nucleus; of serotonin, in the globus pallidus, subthalamic nucleus, and locus ceruleus; and of 5-hydroxyindoleacetic acid, in the globus pallidus, subthalamic nucleus, and nuclei raphe centralis inferior and obscurus. The level of homovanillic acid showed little consistent change in the regions examined. We conclude that some of these monoamine changes, especially the pronounced apparent disturbance of noradrenergic brain mechanisms, may represent a basic neurochemical abnormality in dystonia musculorum deformans and may thus be relevant to the pathoneurophysiology and treatment of this disorder.

Acetyltransferases↗
PubMed1986

Opioid peptides in Huntington's disease: alterations in prodynorphin and proenkephalin system.

The concentrations of dynorphin A1-8 and Met-enkephalin-Arg6-Gly7-Leu8 were measured in the basal ganglia of postmortem brains from patients with Huntington's disease (HD) and from control subjects. A significant reduction of dynorphin A1-8 concentration was found in caudate nucleus, putamen, external globus pallidus and substantia nigra of HD brains. Levels of Met-enkephalin-Arg6-Gly7-Leu8 were reduced in HD caudate nucleus, putamen, internal and external globus pallidus. These data indicate that both the prodynorphin and proenkephalin opioid peptide system are affected in the basal ganglia in HD.

Basal Ganglia↗
PubMed1986

Elevated gamma-aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson's disease: correlation with striatal dopamine loss.

We measured the concentration of gamma-aminobutyric acid (GABA), glutamic acid, and o-phosphoethanolamine in autopsied brain of 9 patients who died with idiopathic Parkinson's disease and 10 control subjects. In the control striatum GABA showed an uneven rostrocaudal distribution pattern with rostral subdivisions containing about 40 to 50% higher levels. When compared with controls, GABA concentrations in Parkinson's disease striatum were generally elevated. The GABA elevation was most pronounced in the caudal subdivision of the putamen; this striatal subdivision also showed the most severe dopamine loss. We observed in the caudal putamen a significant negative correlation between the (elevated) GABA and (reduced) dopamine levels (the latter expressed as the sum of dopamine plus 3-methoxytyramine). Milder nonsignificant elevations of GABA levels were observed in intermediate and rostral putamen followed by the caudate head subdivisions. GABA levels were normal in all extrastriatal brain areas examined. Striatal glutamic acid levels were markedly elevated in 3 of the 9 patients with Parkinson's disease. We suggest that the altered GABA metabolism in the striatum, especially the putamen, is consequent to the nigrostriatal deficiency in this disorder. This secondary change in striatal GABA function is likely to contribute to the basal ganglia dysfunction produced by the striatal dopamine loss and thus may be related to certain aspects of parkinsonian symptomatology.

Brain Chemistry↗
PubMed1986

Brain glutathione peroxidase in neurodegenerative disorders.

Glutathione peroxidase is an enzyme that couples the oxidation of reduced glutathione to the detoxification of peroxides. Alterations in the activity of this component of the glutathione oxygen scavenging system in brain have been reported in several conditions associated with oxidative challenge and/or cellular damage. We measured the activity of glutathione peroxidase in autopsied brain regions of neurologically normal adults and in brain of patients with primary degenerative disorder Alzheimer's type (AD/SDAT), as well as two other neurodegenerative disorders, namely Huntington's disease and striatonigral degeneration. No significant alterations in enzyme activity were observed in morphologically normal or abnormal brain regions. Our results suggest that in the three brain disorders studied, the neuronal cell loss is unlikely to result from reduced activity of brain glutathione peroxidase, and that a significant compensatory increase in this brain enzyme, consequent to the degenerative processes, does not occur.

Aged↗
PubMed1985

Glutathione peroxidase activity in Parkinson's disease brain.

Glutathione peroxidase is an enzyme of major importance in the detoxification of peroxides in brain. Using the spectrophotometric procedure of Paglia and Valentine [8] and Beutler [2] we measured the activity of this enzyme in autopsied brain from 12 patients dying with idiopathic Parkinson's disease and 11 neurologically normal adults matched with respect to age and postmortem interval. In the Parkinson's disease patients glutathione peroxidase activity was slightly but significantly reduced in several brain areas including substantia nigra. Although the magnitude of the glutathione peroxidase deficiency in Parkinson's disease substantia nigra was small (19% reduction), coupled with the reported marked deficiency of reduced glutathione [9] it may represent one of the contributing factors leading to nigral dopamine neurone loss.

Aged↗