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Biomedical subjects

Y Agid

Publications and source records attributed to Y Agid.

At least 451 records · Page 25Linked to original sources
PubMed1989

Cognitive slowing in Parkinson's disease fails to respond to levodopa treatment: the 15-objects test.

To evaluate clinically the slowing of cognitive processing in Parkinson's disease, we used a visual discrimination task consisting of 15 superimposed images of objects. The time needed to identify 12 objects increased by 58% in 70 patients withdrawn from levodopa treatment compared with 20 controls matched for age and education. Perceptual, motor, and psycholinguistic factors, as well as mood, only partially accounted for the slowness of performance. The 15-objects test scores of the parkinsonian patients correlated significantly with both their intellectual impairment and the severity of their parkinsonian disability, but not with the duration of the disease. The scores did not correlate with depression. Levodopa had no effect on the score, although the parkinsonian motor disability score was improved by 54%. The results indicate a cognitive slowing in Parkinson's disease which is probably related to abnormalities of nondopaminergic neuronal systems in the brain.

Adolescent↗
PubMed1988

[3H]GBR 12935 binding to dopamine uptake sites: subcellular localization and reduction in Parkinson's disease and progressive supranuclear palsy.

[3H]GBR 12935 bound with high affinity to dopamine uptake sites in rat striatum where a close parallelism was observed between the subcellular localization profiles for [3H]dopamine uptake and [3H]GBR 12935 specific binding. Using the same ligand, we characterized the dopamine uptake sites in human striatum: the mean KD value was 3.2 nM and the specific binding was inhibited by several dopamine uptake blockers but with slightly lower affinities than those observed in the rat. The subcellular localization profile revealed a synaptosomal enrichment of the specific binding in human striatum. [3H]GBR 12935 binding was decreased in the putamen and caudate nucleus of subjects with Parkinson's disease (33 and 46% of control values, respectively) and progressive supranuclear palsy (38 and 57% of control values, respectively). It is very unlikely that the remaining binding sites in both diseases correspond to piperazine acceptor sites that are not involved in dopamine uptake. However, we cannot exclude the possibility that some of these remaining dopamine transporter sites are not functional, since the reduction in [3H]GBR 12935 specific binding was less marked than the decrease in the dopamine content of the same areas.

Animals↗
PubMed1988

Benzodiazepine receptors in normal human brain, in Parkinson's disease and in progressive supranuclear palsy.

Benzodiazepine receptors have been characterized in human brain. They have been localized mainly in the cerebral cortex and a synaptosomal enrichment was observed after brain fractionation by differential centrifugation. Benzodiazepine receptors were studied in Parkinson's disease and in progressive supranuclear palsy (PSP). In both diseases, the [3H]flunitrazepam specific binding was unchanged when compared to control groups (Bmax and KD values) except in the caudate nucleus of parkinsonian patients where an increase of the specific binding was observed. The subcellular distribution profile of benzodiazepine receptors in Parkinson's disease was similar to that of controls. gamma-Aminobutyric acid (GABA) still enhanced the [3H]flunitrazepam-specific binding (increase of binding affinity), indicating that the functional link between GABA and benzodiazepine receptors remained intact in Parkinson's disease. The present results suggest that benzodiazepine receptors in human striatum are localized on neuronal elements which do not degenerate in Parkinson's disease and PSP.

Aged↗
PubMed1988

Characterization of two antigens in parkinsonian Lewy bodies.

Two antigens, G7 and G9, which are labelled by monoclonal antibodies in Lewy bodies in brains from patients with Parkinson's disease, were characterized by two-dimensional electrophoresis, followed by electroblotting, in order to explore their possible relationship with neuronal degeneration in this disease. The G7 antigen was found in the substantia nigra of subjects with Parkinson's disease and progressive supranuclear palsy, as well as in normal subjects. It was also found in the dopaminergic nucleus paranigralis and the locus coeruleus. The G9 antigen was found in the substantia nigra and locus coeruleus, but also in the caudate nucleus, terminal region of the nigrostriatal dopaminergic neurons, and in the cortex and cerebellum, terminal regions of the noradrenergic neurons in the locus coeruleus. The identity of the antigens remains unknown. They do not correspond to tyrosine hydroxylase or neurofilaments previously detected in Lewy bodies, or to other cytoskeletal proteins. Nor are they related to the presence of neuromelanin in the cells that degenerate in Parkinson's disease. The proteins, or at least the epitopes labelled by the antibodies, are found in normal brain, suggesting that these proteins do not play a causal role in the formation of the Lewy bodies in degenerating neurons in Parkinson's disease. The G7 antigen is absent from the cholinergic substantia innominata, where Lewy bodies are also found, indicating that these antigens are not essential for the formation of the corpuscle.

Antigens↗
PubMed1988

Slowing of cognitive processing in progressive supranuclear palsy. A comparison with Parkinson's disease.

To investigate central processing time in patients with progressive supranuclear palsy and Parkinson's disease, reaction times were measured using tasks with different levels of cognitive complexity but with the same motor response. In patients with Parkinson's disease, the additional central processing time required for more complex situations was no different from that in control subjects, suggesting that cognitive aspects of the reaction time procedures tested were possibly too simple to reveal a slowing of thought processes in these patients. Conversely, the central processing time was increased in patients with progressive supranuclear palsy compared with both Parkinson's disease and control subjects. The increase was associated with impairment in frontal lobe test performance. These results confirm that a slowing of central processing is a prominent feature of the cognitive disturbances of progressive supranuclear palsy and, furthermore, suggest that this slowing may be related to striatofrontal dysfunction.

Aged↗
PubMed1988

Decrease of serotonin-S2 receptors in temporal cortex of patients with Parkinson's disease and progressive supranuclear palsy.

The number of serotonin-S2 receptors was decreased in the temporal cortex of patients with Parkinson's disease and progressive supranuclear palsy (PSP). There was no significant modification of these receptors in the frontal cortex or in the hippocampus and putamen in both diseases. The decrease in number of receptors in PSP was unexpected, because the cerebral cortex is thought to be spared in this disease. There was no correlation between the decrease in number of serotonin-S2 receptors and the degree of dementia in Parkinson's disease, suggesting that these receptors are not directly involved in the deterioration of cognitive functions.

Aged↗
PubMed1988

D1 and D2-type dopamine receptors in patients with Parkinson's disease and progressive supranuclear palsy.

The densities of D1- and D2-type dopamine receptors were measured with [3H]SCH23390 and [3H]spiperone, in the caudate nucleus and putamen of a large series of patients with Parkinson's disease or progressive supranuclear palsy, in relation to markers of dopaminergic and cholinergic innervation of the striatum ([3H]dihydrotetrabenazine binding and choline acetyltransferase activity). Correlations were sought between these parameters and clinical characteristics of the patients (abnormal involuntary movements, dementia, confusional syndrome or treatment). In Parkinson's disease, the densities of both types of receptors were unchanged, whereas in PSP, the density of D2, but not D1-type dopamine receptors, was decreased in the caudate nucleus and the putamen. No correlations between the biochemical and clinical data were found.

Adenylyl Cyclases↗
PubMed1988

Somatostatin concentrations and binding sites in human frontal cortex are differentially affected in Parkinson's disease associated dementia and in progressive supranuclear palsy.

Somatostatin (SRIF) binding sites were characterized in membrane preparations from post mortem human brain tissues using 125I-Tyr0-D-Trp8-SRIF as a ligand. Density of binding sites were high in subiculum and cortex, moderate in temporal cortex, hippocampal formation and hypothalamus and low in putamen. No correlation was observed with the regional distribution of SRIF levels as measured by RIA. Pharmacological characterization, in frontal cortex preparations, revealed that 125I-Tyr0-D-Trp8-SRIF binding was heterogenous and fitted best with a two sites model. 125I-Tyr0-D-Trp8-SRIF binding was guanine nucleotide dependent. Cortical 125I-Tyr0-D-Trp-8-SRIF binding was not different from controls in non-demented or demented parkinsonians and in patients with progressive supranuclear palsy. On the contrary, SRIF levels were significantly decreased in demented parkinsonians.

Aged↗
PubMed1988

Levels of Met-enkephalin, Leu-enkephalin, substance P and cholecystokinin in the brain of the common marmoset following long term 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine treatment.

Common marmosets were treated daily with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 7-9 mg/kg i.p.) for 25 days, and then kept out of drug for three months before biochemical measurements in various brain areas. This treatment induced a dramatic fall (-80%) in dopamine, homovanillic acid and dihydroxyphenylacetic acid levels in the putamen and caudate nucleus, and a significant but less pronounced reduction (less than or equal to 50%) in the levels of these compounds in the nucleus accumbens. In contrast, the concentrations of four neuropeptides: met-enkephalin, leu-enkephalin, substance P, and cholecystokinin, remained unaltered in all brain areas examined in MPTP-treated marmosets. Therefore the neuropeptide alterations previously reported in Parkinson's disease are probably not secondary to the severe lesion of dopaminergic neurones, but constitute another intrinsic feature of the disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Biochemical mapping of cholecystokinin-, substance P-, [Met]enkephalin-, [Leu]enkephalin- and dynorphin A (1-8)-like immunoreactivities in the human cerebral cortex.

The distribution of immunoreactive cholecystokinin, substance P, [Met]enkephalin, [Leu]-enkephalin and dynorphin was determined in the cerebral cortex of the human brain post mortem. Peptide radioimmunoassays in three selected zones of the cortical gray mantle (frontal, temporal, occipital) revealed significant regional differences, prompting to the development of a new dissection procedure for the complete mapping of peptide-like materials throughout the entire cerebral cortex. For this purpose, frozen cerebral hemispheres were cut rostrocaudally in 21 verticofrontal serial sections, from which the cortical gray matter was divided into 4-5 distinct zones. The peptides could be measured in each of the 93 dissected pieces of tissue, but their distribution was uneven. The most abundant was cholecystokinin, particularly in the anterior part of the frontal lobe and in the temporal cortex, where its levels reached 0.5 ng/mg of tissue. The regional distribution of cholecystokinin resembled that of substance P with a decreasing gradient from the frontal to the occipital pole, but absolute levels of substance P were hardly one tenth of cholecystokinin levels. The mean concentrations of the three opioid peptides were even less than those of substance P, and their regional distributions were markedly different. [Met]Enkephalin was concentrated in the occipital cortex, and [Leu]enkephalin in the temporal cortex. Dynorphin was the least abundant, even in the temporal cortex where the highest levels were found. The widespread and heterogeneous distribution of these peptides strongly suggests that each of them exerts specific functions in the human cerebral cortex.

Aged↗
PubMed1988

[3H]dihydrotetrabenazine, a new in vitro monoaminergic probe for human brain.

The monoamine transporter of dopamine (DA), noradrenaline, and 5-hydroxytryptamine synaptic vesicles was assayed in rat and human brain homogenates by in vitro binding of [3H]dihydrotetrabenazine. [3H]Reserpine, a second ligand of the vesicular monoamine transporter, could not be used. [3H]Dihydrotetrabenazine binding in rat brain was stable after 72 h at 22 degrees C postmortem. In major human brain regions, [3H]dihydrotetrabenazine binding was specific and saturable (KD, 2.7 nM). Displacement constants by substrates or inhibitors of vesicular monoamine uptake, and regional distribution in human brain were similar to those found in rodents. The highest densities of binding sites were observed in caudate nucleus, putamen, and accumbens nucleus. In caudate nucleus and in putamen from normal human subjects, [3H]dihydrotetrabenazine binding and homovanillic acid concentration were significantly or nearly significantly correlated. A weaker correlation was found between [3H]dihydrotetrabenazine binding and DA, in association with a higher variability of DA. [3H]Dihydrotetrabenazine binding in caudate nucleus and in putamen decreased significantly with age, unlike DA and homovanillic acid concentrations. The results establish [3H]dihydrotetrabenazine as a presynaptic monoaminergic ligand of interest for studies on postmortem human brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Does levodopa aggravate Parkinson's disease?

We studied the possible deleterious effect of levodopa therapy on 185 patients with Parkinson's disease and concluded that the time when levodopa is introduced, the daily dose, and the duration of treatment do not aggravate Parkinson's disease. We also studied 72 parkinsonian patients with levodopa-induced abnormal involuntary movements to see whether early initiation of levodopa therapy affected the time of onset of abnormal involuntary movements. The results suggested that it did not, and that levodopa was started early in these patients because of the severity of their motor disability.

Female↗
PubMed1987

Regional distribution of mu, delta and kappa opioid receptors in human brains from controls and parkinsonian subjects.

The binding properties of mu and delta opioid receptors were investigated in several areas of human brain by using [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol and [3H]Tyr-D-Thr-Gly-Phe-Leu-Thr as respective selective ligands, while the totality of opioid receptors was measured by using [3H]etorphine as a non-selective agonist. Receptor densities were highest in cerebral cortex, amygdala and striatum, and lowest in the substantia nigra (pars compacta). In the different brain areas of patients with Parkinson's disease, the density and the proportion of the various opioid receptors were not significantly different from control subjects.

Aged↗
PubMed1987

Brain neuropeptides in progressive supranuclear palsy.

No significant alterations in the levels of Met-enkephalin-, Leu-enkephalin-, cholecystokinin- and substance P-like immunoreactive materials were found in 10 areas of postmortem brains from patients with progressive supranuclear palsy (PSP) when compared to controls. These results are at difference with the marked decrease in the levels of enkephalin-, cholecystokinin- and substance P-like immunoreactive materials previously reported in the basal ganglia of parkinsonian patients. Since PSP and Parkinson's disease are both characterized by a severe dopamine nigrostriatal deficit, these results suggest that the decreased brain peptide concentrations found in Parkinson's disease do not simply result from a dopaminergic neuronal loss.

Aged↗
PubMed1987

Nerve cell death in degenerative diseases of the central nervous system: clinical aspects.

The origin of degenerative diseases of the central nervous system lies in genetic and acquired disorders. Analysis of the clinical characteristics of diseases affecting specific neuronal systems may help us to understand their pathogenesis. The stereotyped symptomatology characteristic of most degenerative diseases results from neuronal death in specific pathways: pyramidal tract and motor neurons in amyotrophic lateral sclerosis, nigrostriatal dopamine system in Parkinson's disease, posterior and lateral columns of the spinal cord in Friedreich's ataxia, etc. This suggests that these neurons are sensitive to pathological processes that are still unknown. Progression of the disease, whether linear or not, is slow, but it is more rapid than similar effects due to ageing. This indicates either that the environmental cause of degeneration (if it exists) is continuously present or that a vital process has been once and for all disrupted, perhaps at the level of the genome, causing insufficient production of essential proteins, or accumulation of eventually toxic metabolites. Symptoms generally appear during adulthood, i.e. after normal differentiation has taken place, and after a considerable number of neurons have already been damaged. The initiation of neuronal death precedes the appearance of the first symptoms.

Adult↗