Dopamine D3 receptor is decreased and D2 receptor is elevated in the striatum of Parkinson's disease.
Identifieur interne : 005028 ( Ncbi/Checkpoint ); précédent : 005027; suivant : 005029Dopamine D3 receptor is decreased and D2 receptor is elevated in the striatum of Parkinson's disease.
Auteurs : H L Ryoo [États-Unis] ; D. Pierrotti ; J N JoyceSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1998.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Receptors, Dopamine D2, Tyrosine 3-Monooxygenase.
- pathology : Corpus Striatum, Parkinson Disease.
- Aged, Aged, 80 and over, Autoradiography, Brain Mapping, Female, Humans, Male, Middle Aged, Radioligand Assay, Receptors, Dopamine D3.
Abstract
The mesolimbic dopamine (DA) system preferentially innervates the D3 receptor, whereas the D2 receptor is, in addition, a target of the nigrostriatal DA system. In human brain D3 receptors and D3 mRNA-expressing neurons are largely segregated to brain regions that are the targets of the mesolimbic DA system and the efferents of the "limbic striatum." Thus, D3 receptors may regulate effects of DA on the "limbic" cortico-striatal-pallidal-thalamic-cortical loop. The nigrostriatal DA system is considerably more damaged in Parkinson's disease (PD) than the mesolimbic DA system. We report here, using radioligands selective for the D2 and D3 receptor, that these receptors are independently changed in PD. Tissue collected at autopsy from nine subjects with a diagnosis of PD and eight age-matched subjects with no evidence of a neurologic disorder was processed for [125I]epidepride binding to D2 receptors, [125I] trans-7-OH-PIPAT binding to D3 receptors, [125I]RTI-55 for the DA transporter (DAT), and immunoautoradiography for tyrosine hydroxylase (TH) using autoradiographic methods. Dopaminergic innervation to the caudal putamen was profoundly reduced and to a lesser extent in the rostral putamen in PD. DAT sites but not TH protein levels were reduced in the nucleus accumbens (NAS) in PD compared with age-matched control subjects. This is consistent with a loss of dopaminergic innervation from the mesolimbic DA system but elevation in TH production. D3 receptors were significantly reduced in PD by 40-45% particularly in the NAS and putamen. D2 receptors were elevated in PD in the dorsal putamen by 15%. The reduction in D3 receptor number was not observed in PD cases with a diagnosis of less than 10 years. The changes in DA D3 receptor number is interesting in light of the development of antiparkinsonian agents that are D3-preferring agonists.
DOI: 10.1002/mds.870130506
PubMed: 9756147
Affiliations:
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pubmed:9756147Le document en format XML
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<affiliation wicri:level="1"><nlm:affiliation>Thomas H. Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, Sun City, Arizona 85372, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Thomas H. Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, Sun City, Arizona 85372</wicri:regionArea>
<wicri:noRegion>Arizona 85372</wicri:noRegion>
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<author><name sortKey="Pierrotti, D" sort="Pierrotti, D" uniqKey="Pierrotti D" first="D" last="Pierrotti">D. Pierrotti</name>
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<author><name sortKey="Joyce, J N" sort="Joyce, J N" uniqKey="Joyce J" first="J N" last="Joyce">J N Joyce</name>
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<series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title>
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<front><div type="abstract" xml:lang="en">The mesolimbic dopamine (DA) system preferentially innervates the D3 receptor, whereas the D2 receptor is, in addition, a target of the nigrostriatal DA system. In human brain D3 receptors and D3 mRNA-expressing neurons are largely segregated to brain regions that are the targets of the mesolimbic DA system and the efferents of the "limbic striatum." Thus, D3 receptors may regulate effects of DA on the "limbic" cortico-striatal-pallidal-thalamic-cortical loop. The nigrostriatal DA system is considerably more damaged in Parkinson's disease (PD) than the mesolimbic DA system. We report here, using radioligands selective for the D2 and D3 receptor, that these receptors are independently changed in PD. Tissue collected at autopsy from nine subjects with a diagnosis of PD and eight age-matched subjects with no evidence of a neurologic disorder was processed for [125I]epidepride binding to D2 receptors, [125I] trans-7-OH-PIPAT binding to D3 receptors, [125I]RTI-55 for the DA transporter (DAT), and immunoautoradiography for tyrosine hydroxylase (TH) using autoradiographic methods. Dopaminergic innervation to the caudal putamen was profoundly reduced and to a lesser extent in the rostral putamen in PD. DAT sites but not TH protein levels were reduced in the nucleus accumbens (NAS) in PD compared with age-matched control subjects. This is consistent with a loss of dopaminergic innervation from the mesolimbic DA system but elevation in TH production. D3 receptors were significantly reduced in PD by 40-45% particularly in the NAS and putamen. D2 receptors were elevated in PD in the dorsal putamen by 15%. The reduction in D3 receptor number was not observed in PD cases with a diagnosis of less than 10 years. The changes in DA D3 receptor number is interesting in light of the development of antiparkinsonian agents that are D3-preferring agonists.</div>
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