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Striatal cholinergic cell ablation attenuates L-DOPA induced dyskinesia in Parkinsonian mice.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Won, Lisa A. Ding, Yunmin Singh, Pardeep Kang, Un Jung |
| Copyright Year | 2014 |
| Abstract | 3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia (LID) is a debilitating side effect of long-term dopamine replacement therapy in Parkinson's Disease. At present, there are few therapeutic options for treatment of LID and mechanisms contributing to the development and maintenance of these drug-induced motor complications are not well understood. We have previously shown that pharmacological reduction of cholinergic tone attenuates the expression of LID in parkinsonian mice with established dyskinesia after chronic L-DOPA treatment. The present study was undertaken to provide anatomically specific evidence for the role of striatal cholinergic interneurons by ablating them before initiation of L-DOPA treatment and determining whether it decreases LID. We used a novel approach to ablate striatal cholinergic interneurons (ChIs) via Cre-dependent viral expression of the diphtheria toxin A subunit (DT-A) in hemiparkinsonian transgenic mice expressing Cre recombinase under control of the choline acetyltransferase promoter. We show that Cre recombinase-mediated DT-A ablation selectively eliminated ChIs when injected into striatum. The depletion of ChIs markedly attenuated LID without compromising the therapeutic efficacy of L-DOPA. These results provide evidence that ChIs play a key and selective role in LID and that strategies to reduce striatal cholinergic tone may represent a promising approach to decreasing L-DOPA-induced motor complications in Parkinson's disease. |
| Starting Page | 272 |
| Ending Page | 276 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.jneurosci.org/content/jneuro/34/8/3090.full.pdf |
| PubMed reference number | 24553948v1 |
| Alternate Webpage(s) | https://doi.org/10.1523/JNEUROSCI.2888-13.2014 |
| DOI | 10.1523/jneurosci.2888-13.2014 |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Volume Number | 34 |
| Issue Number | 8 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 2'-Deoxythymidine Ablation Acyltransferase Alanine Transaminase Choline Contribution Diphtheria Toxin Dopa Dopamine Dyskinesia, Drug-Induced Dyskinetic syndrome Interneurons Levodopa Motor Neuron Disease Neostriatum Non-Neuronal Cholinergic System Parkinson Disease Parkinsonian Disorders Pharmacology recombinase |
| Content Type | Text |
| Resource Type | Article |
