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Biomedical subjects

Y Agid

Publications and source records attributed to Y Agid.

592 records · Page 33Linked to original sources
PubMed1973

Monoamine oxidase and aldehyde dehydrogenase activity in the striatum of rats after 6-hydroxydopamine lesion of the nigrostriatal pathway.

Monoamine oxidase and aldehyde dehydrogenase activity were significantly reduced in the striatum of rats 8 days after lesion of the nigrostriatal nerve pathway caused by 6-hydroxydopamine. Evidence is presented for the existence of an intraneuronal 'dopamine monoamine oxidase' and intraneuronal aldehyde dehydrogenase. Dopamine concentrations were reduced to 10% of their control values.

Aldehyde Oxidoreductases↗
PubMedDate not supplied

Neurotrophin receptors and selective loss of cholinergic neurons in Alzheimer disease.

The most consistent neuropathological finding in Alzheimer disease (AD) is the loss of cholinergic neurons of the nucleus basalis of Meynert (NbM). Using immunohistochemistry, we have previously shown that cholinergic neurons located in the ventral striatum were affected, whereas those of the caudate nucleus, putamen, and mesencephalon were spared. Since cholinergic neurons that degenerate in AD are sensitive to NGF and those that are spared are not, it has been hypothesized that the loss of neurotrophins receptors may play a role in the death of cholinergic neurons in AD. Using immunohistochemistry, we have detected the presence of TrkA on most cholinergic neurons from the NbM, on some from those of the striatum, but not on those of the mesencephalon in the human brain. In AD patients, the number of neurons that expressed TrkA was markedly decreased in the NbM very likely as a consequence of cholinergic neuronal loss. In the striatum, despite the loss of high-affinity NGF binding previously reported, no loss of TrkA was observed. Taken together, these results suggest a decreased expression of NGF receptors on the striatal cholinergic neurons in AD. This loss may contribute, when it reaches a crucial threshold, to the death of cholinergic neurons occurring in AD.

Alzheimer Disease↗
PubMedDate not supplied

Regional distribution of vasoactive intestinal peptide in brains from normal and parkinsonian subjects.

The distribution of vasoactive intestinal peptide (VIP) in the post-mortem human brain was determined by radioimmunoassay using a highly specific antiserum. The detection limit of the assay was 4 fmol/tube. The highest concentrations of VIP were found in the cerebral cortex, amygdala, hypothalamus and hippocampus. The lowest levels of peptide were detected in basal ganglia including caudate nucleus, external pallidum, putamen and substantia nigra. All dilution curves of acetic acid extracts from different brain areas were strictly parallel to the standard curve. Sephadex G-50 gel filtration of frontal cortex extract showed that VIP-like immunoreactivity (VIP-LI) eluted as a major peak comigrating with synthetic hVIP. Detailed mapping of VIP in the human cerebral cortex showed the existence of a rostro-caudal gradient of VIP-LI concentrations: the frontal cortex exhibited the highest VIP levels, the parietal and temporal cortex contained medium values and the occipital cortex contained the lowest VIP levels. The concentrations of VIP-LI were compared in various regions of the human brain from normal and parkinsonian subjects. No significant changes in VIP-LI levels occurred in the brains of patients dying with Parkinson's disease. No difference in VIP levels could be found either when the parkinsonian group was subdivided into nondemented and demented patients. These data indicate that VIP-containing neurons are not affected in parkinsonian patients. Our results also suggest that VIP neuronal systems are not involved in the course of dementing process in Parkinson's disease.

Aged↗
PubMedDate not supplied

Linkage analyses between dominant X-linked Charcot-Marie-Tooth disease, and 15 Xq11-Xq21 microsatellites in a new large family: three new markers are closely linked to the gene.

X-linked dominant inheritance was suspected in a large family with Charcot-Marie-Tooth disease since no male to male transmission was observed, and since the sensory and motor neuropathy was more severe in males than in females. To test linkage to the dominant X-linked Charcot-Marie-Tooth disease (DCMTX) locus in Xq13, genotypes of 19 affected and 19 unaffected individuals from this family were determined for 4 microsatellite markers. Close linkage to mfd66 (DXS453) was found by bipoint analysis (Zmax = 4.8 at theta = 0.00). Multipoint analysis mapped the gene between the androgen receptor and DXYS1. In addition, linkage analysis performed with 11 microsatellite markers, derived from a high density map spanning 16 cM on Xq11-Xq21 revealed 3 new tightly linked loci: afm287zg1 (DXS1216), afm261zh5 and afm207zg5 (DXS995). Multipoint analysis localized the DCMTX gene to a 7.5 cM interval between afm123xd4 (DXS988) and afm116xg1 (DXS986). Combined analysis with these new microsatellites provides a powerful tool for carrier detection because of their high informativity and the small genetic distance (< 10 cM) between the markers flanking the gene.

Blotting, Western↗
PubMedDate not supplied

Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease.

The alpha-synuclein gene (SNCA) has been implicated in autosomal dominant forms of Parkinson's disease. We screened 119 individuals from families with this rare form of the disease for SNCA duplications by semiquantitative multiplex PCR. Two patients had duplications, which were confirmed by analysis of intragenic and flanking microsatellite markers. The phenotype in both patients was indistinguishable from idiopathic Parkinson's disease and no atypical features were present, by contrast with reports of families with triplication of the same gene. These results indicate that SNCA is more frequently associated with familial Parkinson's disease than previously thought, and that there is a clear dosage effect according to the number of supernumerary copies of this gene.

Adult↗
PubMedDate not supplied

Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease.

The neuropeptides neurokinin B, neurotensin, and anandamide, the endogenous ligands of NK3, NT1, and CB1 receptors respectively, are known to interact with brain dopaminergic transmission. This study evaluated the effects of these three antagonists of the NK3 (SR 142801), neurotensin (SR 48692), and cannabinoid (SR 141716) receptors on the severity of motor symptoms and levodopa-induced dyskinesias after administration of a single dose of levodopa in 24 patients with Parkinson disease. In this exploratory randomized, double-blind, placebo-controlled study, at the dose used, the drugs tested were well tolerated and could not improve parkinsonian motor disability.

Aged↗
PubMedDate not supplied

Trk neurotrophin receptors in cholinergic neurons of patients with Alzheimer's disease.

Besides cortical pathology, Alzheimer's disease (AD) is characterized by a loss of cholinergic neurons in the basal forebrain but not in the caudate nucleus, putamen or mesencephalon. Since cholinergic neurons which degenerate in AD are sensitive to nerve growth factor (NGF), a link between NGF sensitivity and the vulnerability of cholinergic neurons has been suspected. Levels of NGF are not altered in patients with AD, however. Thus, cholinergic nerve cell death in AD could not result from a deficiency in NGF receptors. Using sequential immunohistochemistry with antibodies that recognize preferentially TrkA, the specific receptor for NGF, and with antibodies directed against choline acetyltransferase we analyzed the expression of neurotrophin receptors in cholinergic neurons from control and AD brains. TrkA was expressed on cholinergic neurons of the striatum and nucleus basalis of Meynert but not on those of the mesencephalon. In AD patients, the number of neurons expressing TrkA was markedly decreased in the nucleus basalis of Meynert, very likely as a consequence of cholinergic neuronal loss. No loss of TrkA-positive neurons was observed in the striatum. Taken in conjunction with our previously published report of loss of high-affinity NGF binding in the striatum of AD patients, our results suggest a reduced expression of TrkA, the specific receptor for NGF, on striatal cholinergic neurons in AD. The loss of neurotrophin receptors may contribute to the alteration of cholinergic neurons occurring in AD.

Aged↗
PubMedDate not supplied

Chronic thalamic stimulation with three-dimensional MR stereotactic guidance.

PURPOSE: To report a method of electrode implantation in the ventralis intermedius nucleus of the thalamus for the treatment of tremor using a 3-D stereotactic MR imaging technique. METHODS: Five patients (three men and two women; mean age, 59 years) with medically refractory tremor had intrathalamic implantation of a stimulating electrode. Stereotactic MR imaging was performed on a 1.5-T unit equipped with an MR-compatible Leksell G stereotactic frame fixed to the patient's head. Calculation of the coordinates of the theoretical target was based on the coordinates of the anterior commissure, the posterior commissure, and the midline sagittal plane as determined via stereotactic MR imaging. During the surgical procedure, the best position for the stimulating electrode was determined by electrophysiological and clinical studies. Postoperative MR control studies were done in all cases to verify the position of the electrode. RESULTS: Stereotactic MR imaging allowed precise implantation of the stimulating electrode in all patients. Electrode stimulation produced a 90% reduction of the tremor in two patients, an 80% and 70% reduction in one patient each, and a persistent microthalamotomy-like effect in the fifth patient. Examination of the MR control studies showed that mean error in the positioning of the electrodes was 0.77 +/- 0.6 mm (mean +/- SD) in the x direction and 0.80 +/- 1.02 mm in the y direction. CONCLUSION: Although our series is relatively small, the precision achieved with stereotactic MR imaging proves that it can be used with confidence for precise functional neurosurgical procedures.

Brain Mapping↗
PubMedDate not supplied

[Abnormal movements caused by L-DOPA in patients with Parkinson's disease: correlation with the plasma concentrations of DOPA and O-methyl-DOPA].

This study involved twleve parkinsonian patients exposed to abnormal movements provoked by L-DOPA. Including six patients with "mid-dose" dyskinesias and six others with "onset and end of dose" dyskinesias, Correlation between the circumstances of onset of abnormal movements and plasma concentrations of DOPA and O-methyl-DOPA, after administration of a dose of L-DOPA + IDC, gave the following results: 1) mid-dose dyskinesias appeared with the highest plasma concentrations of DOPA, at the maximum therapeutic effect; 2) onset and end of dose occurred during rise and fall in plasma levels of DOPA, coinciding with the relief and the reappearance of parkinsonian symptoms respectively; 3) no correlation could be established between plasma concentrations of O-methyl-DOPA and the duration of the period of clinical remission or of abnormal movements. These biochemical data, completed by the neuropharmacological study of one patient with onset and end of dose abnormal movements suggest the predominant role of a disturbance in central dopaminergic mechanisms in the genesis of abnormal movements, whatever their nature.

Dihydroxyphenylalanine↗
PubMedDate not supplied

Attentional deficits in Parkinson's disease: partial reversibility with naphtoxazine (SDZ NVI-085), a selective noradrenergic alpha 1 agonist.

Several authors have suggested that catecholamine depletion may affect attentional processes in human subjects and could be implicated in the frontal lobe syndrome that has been described in Parkinson's disease (PD). The present study reports the effects of a placebo and naphtoxazine (SDZ-NVI-085), a selective noradrenergic alpha 1 agonist. These substances were administered to nine parkinsonian patients who were assessed on measures of attention, including neuropsychological tests and evoked potentials. The results indicate that naphtoxazine may improve performance on some tests of "frontal functions," including the Stroop and the Odd-Man-Out tests, which have been previously found to be affected in PD. However, the results of some other neuropsychological tests of frontal function were not affected by naphtoxazine. Specific evoked potentials such as the Nd1 and Nd2 curves--which are thought to reflect attentional processes and which have been found to be affected in PD--were improved by naphtoxazine. Finally, naphtoxazine reduced the percentage of errors and restored the lateralization of N100 during the Shifting Reaction Time Task, suggesting that this substance may act on the processes underlying the shifting deficit in these patients. The results are discussed in terms of the specific cognitive processes that may be affected by naphtoxazine and in terms of the role of the noradrenaline in attentional deficits found in PD.

Adrenergic alpha-Agonists↗