Altered D 1 dopamine receptor trafficking in parkinsonian and dyskinetic non-human primates
Dyskinesias represent a debilitating complication of levodopa therapy for Parkinson's disease (PD). While we recently demonstrated that levodopa-induced dyskinesia results from increased dopamine D 1 receptor-mediated transmission, we also questioned the possible role of subcellular localizatio...
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| Vydáno v: | Neurobiology of disease Ročník 26; číslo 2; s. 452 - 463 |
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| Hlavní autoři: | , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
Elsevier Inc
2007
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| Témata: | |
| ISSN: | 0969-9961, 1095-953X |
| On-line přístup: | Získat plný text |
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| Shrnutí: | Dyskinesias represent a debilitating complication of levodopa therapy for Parkinson's disease (PD). While we recently demonstrated that levodopa-induced dyskinesia results from increased dopamine D
1 receptor-mediated transmission, we also questioned the possible role of subcellular localization of D
1 and D
2 receptors in mediating these effects as we previously showed that D
1 receptors undergo differential trafficking in striatal neurons of non-dyskinetic PD patients. Taking advantage of a monkey brain bank, we here report changes affecting the cellular and subcellular distribution of D
1 and D
2 dopamine receptors within the striatum of three experimental groups: normal, parkinsonian and dyskinetic
l-dopa-treated parkinsonian animals. Our studies at both light and electron microscopy levels show a recruitment of D
1 receptor at the plasma membrane of striatal neurons in the parkinsonian animals and a strong increase of D
1 expression both at the membrane and in cytoplasm of dyskinetic animals, whereas D
2 receptor distribution is only modestly affected in all conditions. Our results rule out the hypothesis of a pathological overinternalization of dopamine receptors in levodopa-induced dyskinesia but raise the possibility for involvement of D
1 receptors in the priming phenomenon through massive and sudden internalization in response to the first ever administration of
l-dopa and for an altered homologous desensitization mechanism in dyskinesia leading to an increased availability of D
1 receptors at membrane. Further experiments including parkinsonian monkeys chronically treated with
l-dopa that show no dyskinesia and parkinsonian monkeys treated only once with
l-dopa are now necessary to confirm our hypothesis. |
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| ISSN: | 0969-9961 1095-953X |
| DOI: | 10.1016/j.nbd.2007.02.001 |