Striatal ΔFosB gene suppression inhibits the development of abnormal involuntary movements induced by L-Dopa in rats
Autor: | M. Maral Mouradian, Stella M. Papa, Hideki Mochizuki, Kayoko Fong, Jie Zhang, Goichi Beck |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Dyskinesia Drug-Induced Transgene Biology Pharmacology Article Small hairpin RNA Antiparkinson Agents Levodopa 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation RNA interference Dopamine Genetics medicine Animals Humans Oxidopamine Molecular Biology Gene knockdown Abnormal involuntary movement Corpus Striatum Rats Disease Models Animal 030104 developmental biology Dyskinesia 030220 oncology & carcinogenesis Molecular Medicine medicine.symptom medicine.drug |
Zdroj: | Gene therapy |
ISSN: | 1476-5462 0969-7128 |
Popis: | L-Dopa-induced dyskinesia (LID) is associated with the upregulation of striatal ∆FosB in animal models and patients with Parkinson's disease (PD). A mechanistic role of ∆FosB is suspected because its transgenic overexpression leads to the early appearance of LID in rodents and primates. This study in rodents is aimed at exploring the therapeutic potential of striatal ∆FosB gene suppression to control LID in patients with PD. To determine the effect of reducing striatal ∆FosB expression, we used RNAi gene knockdown in a rat model of PD and assessed abnormal involuntary movements (AIMs) in response to L-Dopa. Rats with dopamine depletion received striatal injections of rAAV-∆FosB shRNA or a control virus before exposure to chronic L-Dopa treatment. The development of AIMs during the entire L-Dopa treatment period was markedly inhibited by ∆FosB gene knockdown and its associated molecular changes. The antiparkinsonian action of L-Dopa was unchanged by ∆FosB gene knockdown. These results suggest a major role for ∆FosB in the development of LID and support exploring strategies to reduce striatal ∆FosB levels in patients with PD. |
Databáze: | OpenAIRE |
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