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Biomedical subjects

Y Agid

Publications and source records attributed to Y Agid.

At least 541 records · Page 30Linked to original sources
PubMed1982

CCK-8-Immunoreactivity distribution in human brain: selective decrease in the substantia nigra from parkinsonian patients.

The regional distribution of immunoassayable CCK-8 was determined in 12 regions of control and parkinsonian human brain, with specific attention to the possible regional coexistence of CCK-8 with dopamine. In Parkinson's disease, CCK-8-I levels were only decreased in the substantia nigra where dopamine cell bodies lie, and not in striatal and corticolimbic dopamine projecting areas. Our results suggest that the major proportion of dopaminergic neurones degenerated in Parkinson's disease may not contain the CCK-8 peptide.

Appetite Depressants↗
PubMed1982

Microtopography of methionine-enkephalin, dopamine and noradrenaline in the ventral mesencephalon of human control and Parkinsonian brains.

The topographical distributions of Met-enkephalin, dopamine and noradrenaline were determined in serial frontal sections of human substantia nigra (pars compacta and pars reticulata) and ventral tegmental area. Met-enkephalin was identified by Biogel and thin layer chromatography and assayed by a specific radioimmunoassay. In the substantia nigra (pars compacta and pars reticulata), the levels of Met-enkephalin increased progressively from the rostral to the caudal part of the structure. This pattern closely resembled that of dopamine levels, particularly in the pars compacta. Noradrenaline levels in the substantia nigra and those of Met-enkephalin, dopamine, and noradrenaline in the ventral tegmental area, exhibited only limited fluctuations from the anterior to the posterior part of each structure. Highly significant decreases in Met-enkephalin, dopamine and noradrenaline levels were observed in the substantia nigra and ventral tegmental area of Parkinsonian brains. This observation, together with the close topographical association of dopamine and Met-enkephalin in the substantia nigra, further supports the likely existence of important functional relationships between dopaminergic and enkephalinergic neurons in the human brain.

Aged↗
PubMed1982

Muscarinic binding and choline acetyltransferase activity in Parkinsonian subjects with reference to dementia.

[3H]Quinuclidinylbenzilate ([3H]QNB) binding and choline acetyltransferase (CAT) activity were studied in post-mortem brains from control and Parkinsonian subjects. CAT levels were reduced in the cortex and hippocampus of Parkinsonians. The apparent affinity of [3H]QNB for the muscarinic receptor was higher in both the caudate nucleus and the frontal cortex. Receptor density increased only in the frontal cortex. These changes are discussed in relation to dementia and mental disturbances following anticholinergic treatment frequently observed in Parkinson's disease.

Aged↗
PubMed1982

Effect of gamma-vinyl GABA in Friedreich's ataxia.

Gamma-Vinyl GABA, an irreversible inhibitor of GABA-transaminase, was administered orally in two daily doses of 250 mg to 10 patients with cerebellar ataxia (9 with Friedreich's ataxia, one with olivo-ponto-cerebellar atrophy) for at least one month in an open study. No significant difference occurred in the disability scores of cerebellar symptomatology for the group as a whole, but seven patients showed some improvement in scores with treatment and two patients claimed marked subjective amelioration. Tolerance to Gamma-Vinyl-GABA treatment was excellent. These preliminary results suggest that further studies with well-tolerated agents which enhance CNS GABA-ergic function are warranted in patients with cerebellar ataxia.

4-Aminobutyrate Transaminase↗
PubMed1982

Concentration gradients of free and total gamma-aminobutyric acid and homocarnosine in human CSF: comparison of suboccipital and lumbar sampling.

Concentrations of free and total gamma-aminobutyric acid (GABA) and homocarnosine were determined in sequential aliquots of the first 30 ml of CSF obtained by lumbar puncture in five patients. Rostrocaudal gradients were calculated and compared to gradients estimated by determining concentrations of these substances in CSF obtained by simultaneous suboccipital and lumbar punctures in four more patients. In the lumbar fractions study, rostrocaudal mean gradients of 0.36, 36, and 21 pmol/ml for free GABA, total GABA, and homocarnosine, respectively, were calculated. In the suboccipital/lumbar study, gradients of 0.33, 30, and 24 pmol/ml for free GABA, total GABA, and homocarnosine, respectively, were estimated. These results indicate that valid comparison of CSF concentrations of these substances is restricted to similar fractions and suggest that in CSF the substances originate largely from brain rather than from peripheral sources.

Adult↗
PubMed1982

Glycine receptors in the human substantia nigra as defined by [3H]strychnine binding.

Specific [3H]strychnine binding was used to identify the glycine receptor macromolecular complex in human spinal cord, substantia nigra, inferior olivary nucleus, and cerebral cortex. In material from control patients a high-affinity KD (3--8 nM) was observed in the spinal cord and the substantia nigra, both the pars compacta and the pars reticulata. This is very similar to the values observed in the rat and bovine spinal cord (8 and 3 nM, respectively) and rat substantia nigra (12 nM). In the human brain the distribution of [3H]strychnine binding (at 10 nM) was: spinal cord = substantia nigra, pars compacta greater than substantia nigra, pars reticulata = inferior olivary nucleus greater than cerebral cortex. The binding capacity (Bmax) of the rat brain (substantia nigra or spinal cord) was approximately 10-fold that of the human brain. [3H]Strychnine binding was significantly decreased in the substantia nigra from Parkinson's disease patients, both in the pars compacta (67% of control) and the pars reticulata (50% of control), but not in the inferior olivary nucleus. The results were reproduced in preliminary experiment in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. In the substantia nigra from patients who died with Huntington's disease, [3H]strychnine binding tended to be high (150% of control, NS) in both the pars compacta and the reticulata. [3H]Strychnine binding was unaltered in the substantia nigra of patients with senile dementia. Together with previous neurophysiological and neuropharmacological findings, those results support the hypothesis of glycine receptors occurring on dopamine cell bodies and/or dendrites in the substantia nigra.

Adult↗
PubMed1982

Enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity: selective radioassay, properties, and regional distribution in human brain.

The compound [3H]Tyr1,D-Ala2,Leu-OH5]enkephalin has been synthesised as a potentially selective substrate for enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity in brain. Incubations in the presence of homogenates and particulate fractions from rodent and human brain result in the formation of [3H]Tyr-D-Ala-Gly, which can be conveniently isolated by polystyrene bead column chromatography. The enzyme activity responsible for the hydrolysis of the Gly3-Phe4 amide bond of this substrate displays close resemblance to that hydrolysing the natural enkephalins at the same level. In addition, enkephalinase activity characterised in postmortem human brain is closely similar to that in rodent brain, with regard to optimal pH and apparent affinities of various substrates and inhibitors, including the potent compound thiorphan. Enkephalinase activity is distributed in a highly heterogeneous fashion among regions of human brain, the highest levels being found in globus pallidus and pars reticulata of the substantia nigra. This distribution is poorly correlated with that of opiate receptor binding sites but displays some resemblance to that of reported Met5-enkephalin levels.

Aged↗
PubMed1982

Confusion, dementia and anticholinergics in Parkinson's disease.

Among a population of 75 hospitalised Parkinsonian subjects, confusional states were observed in 46% of demented patients not receiving anticholinergic drugs and in 93% of demented patients under anticholinergic therapy. The sensitivity of demented Parkinsonians to anticholinergic drugs can be attributed to a cholinergic deficiency which has been detected in the cortex and hippocampus of Parkinsonian patients post-mortem. The observations suggest that anticholinergic medication should be avoided in Parkinsonians with intellectual impairment.

Cognition Disorders↗
PubMed1982

Dopamine deficiency in the cerebral cortex in Parkinson disease.

We measured the concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in several cortical areas from controls and parkinsonian patients. Substantial amounts of dopamine and its metabolites were detected in hippocampus and entorhinal, cingulate, and frontal cortex of controls. In parkinsonian patients the levels of dopamine and its metabolites were reduced in these neocortical areas and hippocampus. Diminution of cortical dopaminergic transmission may play a role in the mental impairment of some Parkinson patients.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

[Effect of a synthetic analog of enkephalin on the choreic syndrome].

A cross-over, double-blind intravenous administration of a single dose of FK 33-824, a rigid analog of enkephalin, was performed in 12 choreic patients (0,5 mg in 6 patients, 2 mg in 6 patients). The number of abnormal involuntary movements per minute and their amplitude was not altered after FK 33-824 when compared to placebo administration. This result however does not exclude the possibility of a functional interaction between Met-enkephalinergic and dopaminergic systems in the human brain.

Adult↗
PubMed1981

Distribution of specific high-affinity binding sites for [3H]imipramine in human brain.

[3H]Imipramine binds with high affinity to membranes from different regions of the human brain. The highest density of binding sites was observed in the hypothalamus and substantia nigra and the lowest density in the white matter and cerebellum. As found in rat brain, tricyclic antidepressant drugs are potent inhibitors of [3H]imipramine binding. Atypical antidepressants are, however, much weaker at inhibiting the specific binding. The [3H]imipramine binding site in human cortex is apparently identical to the site already described in the rat brain and in human platelets.

Aged↗
PubMed1981

Microtopography of tyrosine hydroxylase, glutamic acid decarboxylase, and choline acetyltransferase in the substantia nigra and ventral tegmental area of control and Parkinsonian brains.

Tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD), and choline acetyl transferase (CAT) were used as markers for catecholamine, gamma-aminobutyric acid, and acetylcholine containing neurons in human mesencephalon. Their rostrocaudal, mediolateral, and dorsoventral distribution was investigated within the substantia nigra pars compacta (SNC) and pars reticulata (SNR) and in the ventral tegmental area (VTA). TH activity was highest in the caudal, medial, and ventral SNC and in the middle of VTA medio-ventrally. The enzyme activity in SNR was low and uniformly distributed. In SNC as well as SNR, GAD activity was high and greater laterally and in the middle of the rostro-caudal extent. No particular pattern of distribution was observed in VTA. an area with low GAD content. In the substantia nigra, CAT activity was low. A characteristic medio-ventral distribution with a peak of high enzyme activity in the middle of the rostrocaudal extent was observed. In VTA, enzyme levels were high and also concentrated medio-ventrally and in the middle of the area. In parkinsonian brains, the distribution of TH was uniformly affected throughout the rostro-caudal extent. In VTA the enzyme activity was not as reduced as in SNC and SNR; the CAT pattern was only disrupted in a very localized part of SNC but not in SNR and VTA. In all three areas, GAD activity was reduced to a uniformly low distribution.

Aged↗