Regional distribution of monoamine vesicular uptake sites in the mesencephalon of control subjects and patients with Parkinson's disease : a postmortem study using tritiated tetrabenazine
Identifieur interne : 004876 ( Main/Exploration ); précédent : 004875; suivant : 004877Regional distribution of monoamine vesicular uptake sites in the mesencephalon of control subjects and patients with Parkinson's disease : a postmortem study using tritiated tetrabenazine
Auteurs : F. Thibaut [France] ; B. A. Faucheux [France] ; J. Marquez [France] ; J. Villares [France] ; J. F. Menard [France] ; Yves Agid [France] ; E. C. Hirsch [France]Source :
- Brain research [ 0006-8993 ] ; 1995.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Acetylcholinesterase (metabolism), Aged, Aged, 80 and over, Biogenic Monoamines (metabolism), Catecholamine, Female, Human, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Locus niger, Male, Mesencephalon (anatomy & histology), Mesencephalon (metabolism), Middle Aged, Parkinson Disease (metabolism), Parkinson disease, Receptors, Dopamine (metabolism), Receptors, Neurotransmitter (drug effects), Receptors, Neurotransmitter (metabolism), Receptors, Serotonin (metabolism), Serotonin, Substantia Nigra (anatomy & histology), Substantia Nigra (metabolism), Synaptic vesicle, Tetrabenazine, Tyrosine 3-Monooxygenase (metabolism).
- MESH :
- chemical , drug effects : Receptors, Neurotransmitter.
- chemical , metabolism : Acetylcholinesterase, Biogenic Monoamines, Receptors, Dopamine, Receptors, Neurotransmitter, Receptors, Serotonin, Tyrosine 3-Monooxygenase.
- anatomy & histology : Mesencephalon, Substantia Nigra.
- metabolism : Mesencephalon, Parkinson Disease, Substantia Nigra.
- Aged, Aged, 80 and over, Female, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Male, Middle Aged, Tetrabenazine.
Abstract
The distribution of the vesicular monoamine transporter was investigated post mortem in the human ventral mesencephalon of control subjects (n = 7) and patients with Parkinson's disease (n = 4) using tritiated dihydrotetrabenazine binding and autoradiography. Tritiated dihydrotetrabenazine binding was characterized by a single class of sites with a Kd of 7 nM and a Bmax of 180 fmol/mg of protein in the substantia nigra. Tritiated dihydrotetrabenazine binding sites were heterogeneously distributed in the mesencephalon of control subjects : the density of tritiated dihydrotetrabenazine binding sites was high in the substantia nigra pars compacta, locus coeruleus and nucleus raphe dorsalis, moderate in the ventral tegmental area and low in the substantia nigra pars reticulata and catecholaminergic cell group A8. Within the substantia nigra, a zone with maximal density of tritiated dihydrotetrabenazine binding, two times higher than the mean estimate for the whole substantia nigra pars compacta, was detected in the medial part of the structure. The anatomical organization of the human ventral mesencephalon was analyzed on adjacent sections stained for acetylcholinesterase histochemistry and tyrosine hydroxylase immunohistochemistry. Tritiated dihydrotetrabenazine binding displayed the same characteristic regional pattern of distribution as that observed with tyrosine hydroxylase immunohistochemistry except in the nucleus raphe dorsalis, where no tyrosine hydroxylase immunoreactivity was detected. In parkinsonian brains, the level of tritiated dihydrotetrabenazine binding was dramatically decreased in all regions of the ventral mesencephalon analyzed except in the substantia nigra pars reticulata. In the substantia nigra pars compacta, the reduction was by 55% for the whole structure and by 65% in its medial zone, where binding site density was maximal. In most nigral subsectors analyzed, the decrease in density of tritiated dihydrotetrabenazine binding sites reached the level expected given the loss of tyrosine hydroxylase-positive cells observed. By contrast, the ratio of [3H]dihydrotetrabenazine binding to the number of tyrosine hydroxylase positive neurons was significantly increased in the zone of high [3H]dihydrotetrabenazine binding sites. This relative sparing of tritiated dihydrotetrabenazine binding sites may be due either to the contribution of other monoaminergic neurons such as serotoninergic neurons or more likely to hyperactivity of the still surviving dopaminergic neurons.
Affiliations:
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Le document en format XML
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<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Biogenic Monoamines (metabolism)</term>
<term>Catecholamine</term>
<term>Female</term>
<term>Human</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Immunohistochemistry</term>
<term>Locus niger</term>
<term>Male</term>
<term>Mesencephalon (anatomy & histology)</term>
<term>Mesencephalon (metabolism)</term>
<term>Middle Aged</term>
<term>Parkinson Disease (metabolism)</term>
<term>Parkinson disease</term>
<term>Receptors, Dopamine (metabolism)</term>
<term>Receptors, Neurotransmitter (drug effects)</term>
<term>Receptors, Neurotransmitter (metabolism)</term>
<term>Receptors, Serotonin (metabolism)</term>
<term>Serotonin</term>
<term>Substantia Nigra (anatomy & histology)</term>
<term>Substantia Nigra (metabolism)</term>
<term>Synaptic vesicle</term>
<term>Tetrabenazine</term>
<term>Tyrosine 3-Monooxygenase (metabolism)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Receptors, Neurotransmitter</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Acetylcholinesterase</term>
<term>Biogenic Monoamines</term>
<term>Receptors, Dopamine</term>
<term>Receptors, Neurotransmitter</term>
<term>Receptors, Serotonin</term>
<term>Tyrosine 3-Monooxygenase</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomy & histology" xml:lang="en"><term>Mesencephalon</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Mesencephalon</term>
<term>Parkinson Disease</term>
<term>Substantia Nigra</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged</term>
<term>Aged, 80 and over</term>
<term>Female</term>
<term>Humans</term>
<term>Image Processing, Computer-Assisted</term>
<term>Immunohistochemistry</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Tetrabenazine</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Vésicule synaptique</term>
<term>Locus niger</term>
<term>Catécholamine</term>
<term>Sérotonine</term>
<term>Parkinson maladie</term>
<term>Homme</term>
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<front><div type="abstract" xml:lang="en">The distribution of the vesicular monoamine transporter was investigated post mortem in the human ventral mesencephalon of control subjects (n = 7) and patients with Parkinson's disease (n = 4) using tritiated dihydrotetrabenazine binding and autoradiography. Tritiated dihydrotetrabenazine binding was characterized by a single class of sites with a K<sub>d</sub>
of 7 nM and a B<sub>max</sub>
of 180 fmol/mg of protein in the substantia nigra. Tritiated dihydrotetrabenazine binding sites were heterogeneously distributed in the mesencephalon of control subjects : the density of tritiated dihydrotetrabenazine binding sites was high in the substantia nigra pars compacta, locus coeruleus and nucleus raphe dorsalis, moderate in the ventral tegmental area and low in the substantia nigra pars reticulata and catecholaminergic cell group A8. Within the substantia nigra, a zone with maximal density of tritiated dihydrotetrabenazine binding, two times higher than the mean estimate for the whole substantia nigra pars compacta, was detected in the medial part of the structure. The anatomical organization of the human ventral mesencephalon was analyzed on adjacent sections stained for acetylcholinesterase histochemistry and tyrosine hydroxylase immunohistochemistry. Tritiated dihydrotetrabenazine binding displayed the same characteristic regional pattern of distribution as that observed with tyrosine hydroxylase immunohistochemistry except in the nucleus raphe dorsalis, where no tyrosine hydroxylase immunoreactivity was detected. In parkinsonian brains, the level of tritiated dihydrotetrabenazine binding was dramatically decreased in all regions of the ventral mesencephalon analyzed except in the substantia nigra pars reticulata. In the substantia nigra pars compacta, the reduction was by 55% for the whole structure and by 65% in its medial zone, where binding site density was maximal. In most nigral subsectors analyzed, the decrease in density of tritiated dihydrotetrabenazine binding sites reached the level expected given the loss of tyrosine hydroxylase-positive cells observed. By contrast, the ratio of [<sup>3</sup>
H]dihydrotetrabenazine binding to the number of tyrosine hydroxylase positive neurons was significantly increased in the zone of high [<sup>3</sup>
H]dihydrotetrabenazine binding sites. This relative sparing of tritiated dihydrotetrabenazine binding sites may be due either to the contribution of other monoaminergic neurons such as serotoninergic neurons or more likely to hyperactivity of the still surviving dopaminergic neurons.</div>
</front>
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