Role of striatal ΔFosB in l-Dopa-induced dyskinesias of parkinsonian nonhuman primates.
Proc Natl Acad Sci U S A
; 116(37): 18664-18672, 2019 09 10.
Article
en En
| MEDLINE
| ID: mdl-31455727
ABSTRACT
Long-term dopamine (DA) replacement therapy in Parkinson's disease (PD) leads to the development of abnormal involuntary movements known as l-Dopa-induced dyskinesia (LID). The transcription factor ΔFosB that is highly up-regulated in the striatum following chronic l-Dopa exposure may participate in the mechanisms of altered neuronal responses to DA generating LID. To identify intrinsic effects of elevated ΔFosB on l-Dopa responses, we induced transgenic ΔFosB overexpression in the striatum of parkinsonian nonhuman primates kept naïve of l-Dopa treatment. Elevated ΔFosB levels led to consistent appearance of LID since the initial acute l-Dopa tests. In line with this motor response, striatal projection neurons (SPNs) responded to DA with changes in firing frequency that reversed at the peak of the motor response, and these unstable SPN activity changes in response to DA are typically associated with the emergence of LID. Transgenic ΔFosB overexpression also induced up-regulation of other molecular markers of LID. These results support an autonomous role of striatal ΔFosB in the adaptive mechanisms altering motor responses to chronic DA replacement in PD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Levodopa
/
Proteínas Proto-Oncogénicas c-fos
/
Neostriado
/
Discinesia Inducida por Medicamentos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
/
Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2019
Tipo del documento:
Article