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Biomedical subjects

Y Agid

Publications and source records attributed to Y Agid.

At least 505 records · Page 28Linked to original sources
PubMed1985

Brain glutamate decarboxylase in Parkinson's disease with particular reference to a premortem severity index.

Glutamate decarboxylase (GAD) activity was estimated in various areas of the brain in 21 control and 26 parkinsonian subjects matched for age, postmortem delay and premortem state. Retrospective analysis of clinical data was used to define a premortem severity index (PMSI), scaled from 0 to 6, based upon a semiquantitative estimation of the duration of anoxia (0-3) and hypovolaemia (0-3). A significant correlation was found between GAD activity and PMSI in most regions of the brain. In the prefrontal cortex and caudate nucleus, GAD activity was not correlated with age, postmortem delay, sepsis, being bedridden, or with cachexia. Dosage and duration of drug treatment did not influence striatal or cortical GAD levels. In Parkinson's disease, GAD activity did not differ from controls in many brain areas except in the caudate nucleus, hippocampus and the frontal and occipital cortex. No difference in striatal and cortical GAD activity was observed when 10 control and 9 parkinsonian brains were selected for an optimal premortem state which approximated to sudden death (PMSI less than or equal to 2). GAD activity in the caudate nucleus and prefrontal cortex was not significantly influenced by the duration of L-DOPA treatment or withdrawal, disease duration, or severity of intellectual deterioration. Although the number of samples in certain brain areas was too small to allow a definitive conclusion, these results make it doubtful that GABAergic neurons are damaged in this disease.

Age Factors↗
PubMed1985

Subcortical dementia. Frontal cortex hypometabolism detected by positron tomography in patients with progressive supranuclear palsy.

The dementia associated with progressive supranuclear palsy (PSP) is considered to be subcortical because the cerebral cortex, unlike the subcortical structures, is usually free from major neuropathological lesions; the characteristic symptoms point to a dysfunction of the prefrontal lobe. The regional cerebral metabolic rate of glucose (rCMR Glu) was studied by positron emission tomography and 18F-fluoro-2-deoxyglucose18FDG in 6 patients presumed to have PSP and was compared with values found in 8 control subjects of similar age. The results obtained showed a highly significant rCMR Glu decrease in the prefrontal cortex of our patients. The loss of several subcortical afferents to prefrontal cortex may be responsible for the frontal cortical hypometabolism present in PSP.

Aged↗
PubMed1985

Dopaminergic receptor sites in human brain: positron emission tomography.

Positron emission tomography (PET) and 11C-labeled pimozide were used to study the dopaminergic (DA) receptor sites in the human striatum by comparing the latter with the cerebellum, which lacks DA receptors. Although 11C-pimozide concentration was not different in these two brain structures up to 53 minutes after IV injection (thus implying large nonspecific binding), a significant retention of radioactivity in striatum relative to cerebellum was found in controls but not in subjects pretreated with the unlabeled competitor haloperidol. This suggests that the striatal retention seen in controls was due to specific binding of 11C-pimozide to DA receptor sites, whereas prior occupation of the receptor sites by the unlabeled competitor was achieved in pretreated subjects.

Adult↗
PubMed1985

[In vivo study of central serotoninergic receptors in man using positron tomography].

In an attempt to characterize in vivo the central serotonergic (5-HT2) receptors in humans with positron emission tomography (PET), we have used 11C-labeled-ketanserin, a seratonergic antagonist that has high affinity and selectivity for the 5-HT2 receptors in vitro. Earlier in vivo studies in rats had demonstrated a preferential accumulation of 3H-ketanserin in the frontal cortex relative to cerebellum, in accordance with known differences in density of 5-HT2 receptor in these two brain structures (5-HT2 receptors are dense in frontal cortex and sparse or absent in cerebellum). In rats, tracer accumulation in frontal cortex represented specific binding of 3H-ketanserin to 5-HT2 receptors in vivo as demonstrated by inhibition, saturation, and displacement studies. In 5 control subjects, we found a statistically significant retention of 11C-ketanserin in frontal cortex relative to cerebellum after intravenous injection of a tracer dose of the radioligand, suggesting specific in vivo binding of 11C-ketanserin to frontal cortex. To substantiate this hypothesis, we studied 4 subjects administered unlabeled chlorpromazine (CPZ) intramuscularly in therapeutic amounts (75 mg) two hours before the PET study. Pretreatment with CPZ decreased significantly the retention of 11C-ketanserin by the frontal cortex, indicating that almost total occupation of the ketanserin receptors by CPZ had been achieved prior to the injection of the radioligand. Despite these positive results, both the duration and the magnitude of tracer retention by frontal cortex in control subjects were much smaller than was reported in rats, presumably indicating lower specific binding, higher nonspecific binding, and faster drug metabolism in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1985

[Dementia and Parkinson's disease: biochemical and anatomo-clinical correlation].

Intellectual deterioration may be observed in the course of Parkinson's disease. Since it had been reported that central cholinergic systems degenerate in senile dementia and Alzheimer's disease, we measured the activity of choline acetyltransferase (C.A.T.) and the number of muscarinic receptors in various cortical regions of 12 control subjects and 20 patients and compared these biochemical results with clinical and neuropathological data concerning the patients. Thirteen of the parkinsonian patients showed signs of intellectual decline (moderate in 8, severe in 5) and neuropathological examination of the cortex revealed in 10 cases large number of Alzheimer type senile changes extending beyond the hippocampus. C.A.T. activity was decreased in the cerebral cortex in every patient. The decrease was greater in intellectually deteriorated patients and in the group with numerous senile changes in the cortex. The number of muscarinic receptors was increased in patients that had been treated with anticholinergic drugs until they died, but also in those who had not received these drugs, suggesting and underlying denervation hypersensitivity. In the caudate nucleus, however, neither C.A.T. activity nor muscarinic receptor number was altered, indicating that the cortical cholinergic lesion was specific. Although in most cases dementia in Parkinson's disease was of the Alzheimer type, the case of a demented parkinsonian patient in whom cortical C.A.T. activity was severely decreased, in spite of the absence of cortical histopathological evidence characteristic of Alzheimer's disease, suggests that a parkinsonian dementia different from the Alzheimer type also exists. In Parkinson's disease as in Alzheimer's disease the decrease in C.A.T. activity in the cerebral cortex results from degeneration of the cholinergic neurones in the nucleus of Meynert which projects to the cortex. Although the severity of intellectual deterioration seems in relationship with the extent of degeneration, this could already begin before intellectual impairment is apparent.

Aged↗
PubMed1985

[The L-dopa test in Parkinson's disease].

Seventy parkinsonian patients (mean age: 59.6 +/- 1.2 years; duration of disease: 9 +/- 0.6 years) with severe fluctuations of disability under L-Dopa treatment received a single dose of L-Dopa (200 mg + benserazide, a peripheral decarboxylase inhibitor) after 24-72 h interruption of treatment. The delay and duration of action of a single dose of L-Dopa, and the percentage of improvement of the parkinsonian symptoms were 39 +/- 2 and 162 +/- 6 minutes, and 57 +/- 2 p. 100 respectively. Estimation of the difference between the basal parkinsonian score and the score during maximum clinical improvement under levodopa treatment, and the score under levodopa treatment may reflect the severity of dopaminergic and of non dopaminergic lesions in the brain respectively. Modification of the treatment to obtain continuous clinical improvement can be performed according to the delay and duration of action of a single dose of L-Dopa.

Aromatic Amino Acid Decarboxylase Inhibitors↗
PubMed1984

Adrenergic receptors in Parkinson's disease.

Alpha 1, alpha 2, beta 1 and beta 2 adrenergic receptors were measured in the pre-frontal cortex of parkinsonian patients post-mortem. The number of beta 2 receptors was the same in control and parkinsonian subjects. alpha 1 and beta 1 receptors increased in number, particularly in demented parkinsonian patients, while alpha 2 receptors decreased. The affinity constants were unchanged. The modifications seem to be related to lesion of the noradrenergic pathway from the locus coeruleus to the cortex. The relationship between this lesion and the symptoms of dementia and depression in parkinsonian patients is discussed.

Clonidine↗
PubMed1984

Cortical cholinergic projections from the basal forebrain of the rat, with special reference to the prefrontal cortex innervation.

The topographic organization of cells containing choline-acetyltransferase (CAT) and located within the magnocellular nuclei of the basal forebrain was studied by correlating maximum CAT decrease in one or another cortical region with a given localization of the cell lesions. Lesions were made by using ibotenic acid. Lesions affecting the ventral pallidum decreased CAT activity in the antero-medial prefrontal cortex and lesions of the internal and ventral borders of the pallidum decreased CAT activity in sensori-motor and parieto-temporal cortices. None of these lesions produced a decrease of CAT activity in the hippocampus. These results suggest that it is possible to show the presence of a specific cholinergic projection from the basal forebrain to the medial-associative prefrontal cortex of the rat.

Animals↗
PubMed1984

Characterization and visualization of neurotensin binding to receptor sites in human brain.

The binding of monoiodo [125I-Tyr3]-neurotensin to human brain was characterized and visualized using radioreceptorassay and autoradiographic techniques. Specific binding to homogenates of human substantia nigra at 25 degrees C was maximal at 20 min, reversible and saturable. Scatchard analysis of equilibrium data indicated the existence of two populations of binding sites with Kd values of 0.26 nM and 4.3 nM. Corresponding binding capacities were 26 and 89 fmol/mg of protein. Neurotensin analogs inhibited the binding of iodinated neurotensin with relative potencies that demonstrated the crucial role of the C-terminal hexapeptide portion of neurotensin for binding to its receptors. Autoradiography of human substantia nigra sections incubated with iodinated neurotensin revealed high levels of specific binding in the nucleus paranigralis and substantia nigra, pars compacta, and low levels in the substantia nigra, pars reticulata.

Aged↗
PubMed1984

[3H]spiperone binding in the nigrostriatal system in human brain.

The characteristics of [3H]spiperone binding in human brain were compared in three areas of the nigrostriatal pathway: areas containing the nerve terminals (caudate nucleus, putamen and pallidum); the area containing the cell bodies (substantia nigra pars compacta); the area containing the dendrites (pars reticulata). The affinity constants were calculated from saturation binding curves and from the kinetics of association and dissociation. The pharmacological profiles of the receptors was also established by displacement studies. The affinity constants and pharmacological profiles were similar in the striatum and the substantia nigra, although the latter contained a much smaller number of sites. In the substantia nigra, however, curved Scatchard plots were obtained, indicating that a second lower affinity site binding [3H]spiperone was also present. A considerable proportion (50%) of [3H]spiperone binding to nigral membranes could be displaced by the serotonin antagonist cinanserine , compared to the striatum (20%). The effect of post-mortem conditions on binding levels was studied in the rat. A loss of 20% occurred during the first hours after death, but was stable by 6 h until at least 24 h.

Aged↗
PubMed1984

[3H]spiperone binding, dopamine and HVA concentrations in Parkinson's disease and supranuclear palsy.

The density of D2-type dopamine receptors, measured by the binding of [3H]spiperone was normal in the substantia nigra, caudate nucleus and nucleus accumbens of Parkinsonian subjects and above control levels in the putamen, in spite of massive lesions of the dopaminergic neurons. Dopamine levels were reduced in the putamen, caudate nucleus, and nucleus accumbens by 97, 85 and 68%, respectively and by 78 and 93% in the pars compacta and pars reticulata of the substantia nigra. HVA levels were much less affected suggesting that increased activity of the remaining dopaminergic neurons compensated to some extent for the lesions. Neuroleptic treatment and the presence of dementia in the Parkinsonian subjects affected [3H]spiperone binding and dopamine concentrations. Dopamine and HVA levels in the striatum of subjects with supranuclear palsy indicate that the nigrostriatal system was lesioned to the same degree in this disease as in idiopathic Parkinsonism, but spiperone binding was reduced by half in all the structures studies.

Aged↗
PubMed1984

Local cerebral glucose utilisation in treated and untreated patients with Parkinson's disease.

Using the 18f-fluoro-2-deoxy-d-glucose technique and positron emission tomography (PET), the local cerebral glucose utilisation (1CMRGlc) was measured in four non-demented patients with early-onset, bilateral Parkinson's disease characterised by the predominance of akinesia. The study was done twice, first in the untreated condition, and then after levodopa had been resumed. Despite a marked clinical improvement, we found no alteration in 1CMRGlc between the first and second studies in any of the brain structure analysed. Compared to control values, 1CMRGlc in the basal ganglia was moderately increased in both studies. These essentially negative findings agree with most previous human or animal studies, and indicate that the functional alterations in the central dopaminergic systems of patients with Parkinson's disease have metabolic correlates that are too small to be demonstrated by current PET devices.

Antiparkinson Agents↗
PubMed1984

Biochemistry of the hypothalamus in Parkinson's disease.

We assayed the content of neurotransmitters (or their synthesizing enzymes) and neuropeptides in the hypothalamus of control and parkinsonian brains post mortem. Only dopamine concentrations were lower than normal in Parkinson's disease, suggesting that deficiency in hypothalamic dopamine transmission may play a role in the autonomic and endocrine abnormalities of this disorder.

Aged↗
PubMed1984

Pergolide in the treatment of Parkinson's disease.

Pergolide, a long-acting central dopamine agonist, was used as monotherapy in 16 parkinsonian patients. A mean daily dose of 6.3 mg resulted in 73% improvement of parkinsonian disability. Clinical improvement after acute administration of one dose of pergolide was similar to that observed after levodopa plus a peripheral decarboxylase inhibitor but at a dose 100 times lower (2.2 mg and 200 mg, respectively). The effect lasted twice as long (5 1/2 hours and 2 1/4 hours, respectively).

Adult↗