GABA-dopamine relationship in Parkinson's disease striatum.
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Aged↗
Biomedical subjects
K Shannak
Publications and source records attributed to K Shannak.
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↗
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↗
Brain neurotransmitter abnormalities in neuronal intranuclear inclusion body disorder.
Biochemical markers for the major neurotransmitter systems were measured in the brain of a patient who died with neuronal intranuclear inclusion disease. A severe nigrostriatal dopamine deficiency constitutes the basis for the parkinsonian features in the patient. A marked loss of brain norepinephrine and serotonin was found in the basal ganglia and hypothalamus. Brain amino acid (gamma-aminobutyric acid and glutamate) and cholinergic (choline acetyltransferase activity) systems were either normal or less severely affected.
Adolescent↗
Progressive supranuclear palsy: relationship between extrapyramidal disturbances, dementia, and brain neurotransmitter markers.
Biochemical markers for the major neurotransmitter systems were measured in the brains of 5 patients who had died with neuropathologically confirmed progressive supranuclear palsy. A marked nigrostriatal dopamine deficiency, observed in 4 of the 5 patients, was sufficient to explain the parkinsonian features (especially bradykinesia) observed in patients with progressive supranuclear palsy. Dopamine concentrations, however, were normal in the nucleus accumbens, hypothalamus, and temporal cortex. Brain noradrenalin, serotonin, gamma-aminobutyric acid, and aspartic acid levels were generally normal. Normal brain choline acetyltransferase activity (the marker enzyme for cholinergic neurons) in the 2 patients with severe dementia suggests that, at least in some patients, the cognitive impairment in this disorder is likely to be related to noncholinergic neurotransmitter system changes. The glutamic acid concentration was elevated in many brain areas in 3 of the 5 patients studied.
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Reversible drug-induced parkinsonism. Clinicopathologic study of two cases.
Parkinsonism developed in two patients who were received neuroleptic drugs. In each case the clinical manifestations remitted completely when the offending drug or drugs were discontinued. Histologic examination in each patient disclosed abnormalities characteristic of idiopathic paralysis agitans (IPA). Levels of homovanillic acid were low in both cases, and dopamine (DA) levels were measurably reduced in the striatum in one case. It is postulated that before administration of neuroleptic drugs, both patients had preclinical IPA, which predisposed them to parkinsonism when challenged with DA antagonists. Our observations suggest that some patients with irreversible drug-induced parkinsonism may suffer from IPA and that the reversibility of clinical features does not exclude the presence of subclinical IPA.
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Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome.
Different brain regions were removed post mortem from three patients with the Lesch-Nyhan syndrome and were examined for alterations in hypoxanthine-guanine phosphoribosyl transferase (HGPRT), adenine phosphoribosyl transferase, and biochemical indexes of norepinephrine, dopamine, serotonin, gamma-aminobutyric acid (GABA), and acetylcholine neuron function, as compared with age-matched controls. The level of HGPRT activity in the material from patients with the Lesch-Nyhan syndrome was less than 1 per cent of control levels, whereas adenyl phosphoribosyl transferase was not significantly altered. All biochemical aspects of the function of dopamine-neuron terminals in the striatum (except dihydroxyphenylacetic acid levels) were decreased to 10 to 30 per cent of the control values. Serotonin and 5-hydroxyindoleacetic acid levels were increased, striatal choline acetyltransferase levels were low, and striatal glutamic acid decarboxylase and guanylate cyclase activities were unaltered. The disruption of the balance between the functions of GABA, dopamine, and acetylcholine neurons in the extrapyramidal system probably accounts for some of the symptoms observed in the Lesch-Nyhan syndrome (e.g., choreoathetosis).
Acetylcholine↗
The pallido-subthalamic projection in rat: anatomical and biochemical studies.
Horseradish peroxidase injected into the rat globus pallidus was transported retrogradely to subthalamic nucleus neuronal cell bodies and anterogradely to axon terminals in the subthalamic nucleus. Electron microscopic observations revealed that the labeled axon terminals made symmetrical axosomatic and axo-dendritic synaptic contacts with labeled subthalamic nucleus perikarya and dendrites. Injection of kainic acid in the globus pallidus several days prior to the horseradish peroxidase injection abolished the anterograde but not the retrograde transport of the tracer. This suggested the anterograde labeling observed in the subthalamic nucleus originated from neuronal cell bodies in the globus pallidus. Kainic acid lesions identical to those employed in the above anatomical studies resulted in a loss of neuronal cell bodies throughout the globus pallidus and caused a drop in glutamic acid decarboxsylase and choline acetyltransferase levels in the globus pallidus. Levels of these two enzymes were not changed in the subthalamic nucleus after the globus pallidus kainic acid lesions, but both showed small, statistically significant decreases in the substantia nigra. It was concluded that there is a massive pathway from the globus pallidus to the subthalamic nucleus, which terminates on subthalamic nucleus neurons projecting back to the globus pallidus. Neither gamma-aminobutyric acid nor acetylcholine is the major neurotransmitter in the massive pallido-subthalamic pathway.
Animals↗