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Biomedical subjects

O Hornykiewicz

Publications and source records attributed to O Hornykiewicz.

At least 127 records · Page 7Linked to original sources
PubMed1978

Norepinephrine in chronic paranoid schizophrenia: above-normal levels in limbic forebrain.

In postmortem examination of brains of four patients with chronic paranoid schizophrenia, above-normal norepinephrine levels were measured in the ventral septum, the bed nucleus of the stria terminalis, the nucleus accumbens, and the mammillary bodies. No changes were detected in other limbic forebrain regions, including the hypothalamus and the medial olfactory (preoptic) area. The results point to the possibility of a malfunction of limbic noradrenergic mechanisms in schizophrenia, especially the paranoid variety.

Humans↗
PubMed1978

The role of the corpus striatum in neuroleptic- and narcotic-induced catalepsy.

Lesion experiments (in the rat) were designed to elucidate the function of the corpus striatum in neuroleptic- and narcotic-induced catalepsy, respectively. Bilateral lesions of the corpus striatum were observed to attenuate neuroleptic (CPZ)-induced catalepsy. However, analogous lesions of the corpus striatum potentiated narcotic (morphine)-induced catalepsy. These results suggests that (a) the corpus striatum may be a primary site of action of neuroleptic drugs (such as CPZ) in the production of catalepsy, and (b) narcotic (morphine)-induced catalepsy may not be exclusively mediated by the corpus striatum.

Animals↗
PubMed1978

Cerebrospinal fluid homovanillic acid in cerebral infarction.

Cerebrospinal fluid (CSF) homovanillic acid (HVA) concentration was measured in 39 consecutive cases of hemispheric infarction, 7 cases of brainstem infarction, and in 16 controls. The CSF-HVA level was 38 +/- 15 ng/ml (mean +/- S.D.) in the control patients, 15 +/- 6 ng/ml in patients with brainstem infarcts, and 49 +/- 41 ng/ml in those with hemispheric infarcts. The CSF-HVA levels were decreased in brainstem infarct cases (p less than 0.001) and greatly scattered in patients with hemispheric infarcts (range 4--207 ng/ml) when compared to controls. The decrease of levels of CSF-HVA in brainstem infarct cases may reflect interference with the dopaminergic pathways. CSF-HVA values in hemispheric infarction could not be related to the acuteness, location, nor severity of the lesion. The broad range of CSF-HVA values may be due to the interaction of multiple, as yet unknown factors. These findings suggest that dopamine metabolism is altered in many cases with acute brain infarction.

Adolescent↗
PubMed1977

Distribution of high affinity sodium-independent [3H]gamma-aminobutyric acid [3H]GABA binding in the human brain: alterations in Parkinson's disease.

The regional distribution and properties of the sodium-independent "specific" binding of [3H]GABA to membranes prepared from human brains (control and Parkinsonian patients) have been investigated. The affinity of [3H]GABA for the binding site was similar for human cerebellar cortex (Kd = 3.4 x 10(-7) M) and whole rat brain brain (Kd = 5.1 x 10(-7) M) and was inhibited by bicuculline (ID50 = 2.2 X 10(-5) M). In the normal human brain the cerebellar cortex demonstrated the highest number of binding sites, in accordance with the large number of GABA interneurons in this structure. The hippocampus also displayed a high capacity to bind [3H]GABA, whereas cerebral cortical areas showed a lesser capacity. [3H]GABA binding was similar in many regions of the basal ganglia (amygdala, putamen, caudate or accumbens) but was lower than that for the cortical regions. The binding of [3H]GABA to membranes from the substantia nigra, thalamus and internal or external pallidum was lower than for the above regions. Subcortical white matter did not exhibit specific binding for [3H]GABA. In membranes prepared from Parkinsonian patients [3H]GABA binding was greatly decreased in the substantia nigra, but not in other brain areas examined. From this observation it was concluded that there are [3H]-brain areas examined. From this observation it was concluded that there are [3H]-GABA binding sites on the cell bodies (or dendrites) of the nigral dopamine neurons.

Adult↗
PubMed1977

Noradrenaline distribution insubcortical areas of the human brain.

Spectrofluorimetric assay of noradrenaline (NA) was performed in human postmortem brain material in an attempt to provide a detailed map of the subcortical distribution pattern of NA in the human brain. The concentrations of NA was particularly high in 4 areas of the lower brain stem: the area postrema, the area of the nuclei paranigralis-parabrachialis pigmetosus, the locus coeruleus, and the interpeduncular nucleus. The NA-rich areas of the forebrain were determined to be the hypothalamus, the central amygdaloid nucleus, the nucleus accumbens septi, the medial part of the olfactory area, and the bed nucleus of the straia terminalis. The biochemical mapping of NA is discussed in relation to distribution studies based on the histofluorescence technique.

Autopsy↗
PubMed1977

Dopamine in thelimbic regions of the human brain: normal and abnormal.

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.

Adult↗
PubMed1976

Pharmacological evidence for a selective antidopaminergic action of gamma-hydroxybutyric acid.

D-Amphetamine (Amph) and p-chloroamphetamine (PCA) induced dose-dependent increases in oropharyngeal myocloniform twitch activity (MTA) in rats anesthetized with urethane. In doses of 80-120 mg/kg, gamma-hydroxybutyric acid (GHB) blocked Amph-induced MTA. The blockade was readily surmountable. Pretreatment with reserpine markedly enhanced the myoclonigenic effect of Amph and rendered it insensitive blockade by GHB, 160 mg/kg. PCA and tryptamine also effectively stimulated MTA, but unlike Amph were antagonized by low doses of the serotonin (5-HT) antagonist methysergide. In doses which blocked Amph, GHB failed to antagonize the myoclonigenic effect of PCA. It is concluded that: (a) the actions of Amph and PCA on MTA is less sensitive to GHB blockade than DA-mediated MTA; and (c) the GHB-Amph antagonism may be of a functional nature, i.e. result from a depression of the firing activity of DA neurons produced by GHB. Since reserpinization abolished the GHB effect on Amph-induced MTA, the functional integrity of granular DA binding and releasing mechanisms appears to be a pre-requisite for the antagonism between GHB and Amph.

Animals↗
PubMed1976

Beneficial effects of serotonin precursors in postanoxic action myoclonus.

In two patients with postanoxic action myoclonus, L-tryptophan or a monoamine oxidase inhibitor induced a moderate improvement, but L-5-hydroxytryptophan had greater therapeutic effect. Methysergide, a potent blocker of serotonin receptors, consistently induced a marked deterioration in myoclonus. Pretreatment cerebrospinal fluid 5-hydroxyindoleacetic acid levels were reduced significantly in both patients. These findings suggest that postanoxic action myoclonus likely is associated with insufficient serotonergic activity in the central nervous system. Data are inadequate to determine whether this apparent insufficiency reflects structural changes in 5HT-containing raphe nuclei due to a direct anoxic damage to these structures of functional changes caused by a secondary reduction in the activity of intact serotonergic neurons.

5-Hydroxytryptophan↗
PubMed1975

Brain monoamines and parkinsonism.

In Parkinson's disease there is a derangement of the metabolism of at least 3 major brain monoamines, namely, dopamine (DA), norepinephrine (NE) and serotonin (5-HT). Of these alterations the severe deficiency of DA in the striatum is most characteristic, being (a) found in Parkinsonian syndromes of any etiology and (b) significantly correlated with the degree of cell loss in the substantia nigra, and the severity of the main symptoms. On the basis of neurochemical-clinical correlations Parkinson's disease may be subdivided into (a) an asymptomatic stage during which the striatal DA deficiency may reach a marked degree but can be compensated by the remaining DA neurons, and (b) the stage of decompensation (i.e. clinically manifest disease) which ensues when the depetion of striatal DA reaches 70% or more. L-Dopa's main feature as a specific antiparkinson drug may be seen in its potential to revert the decompensated stage of the disease to the stage of functional compensation. This is in many cases possible because (a) the DA turnover in the remaining DA neurons is increased, providing for a high rate of formation (from L-dopa) and release of DA; (b) the "denervated" striatal receptors are supersensitive to DA; and (c) the newly-formed DA can be expected to reach a wide area of the striatum due to the high degree of divergence of the dopaminergic innervation. Compared with the striatal DA deficiency, the degree of NE and 5-HT decrease in the Parkinsonian brain is moderate. The decrease in NE may be due to the (moderate) cell loss in the locus coeruleus; at present no morphological basis for the lowering of brain 5-HT is known. The functional significance of the changes in brain NE may be an aggravation of akinesia. The decrease in brain 5-HT may be related to aspects of Parkinson's disease in turn related to affective behavior and mood.

Amines↗