| First Author | Won L | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 8 | Pages | 3090-4 |
| PubMed ID | 24553948 | Mgi Jnum | J:220644 |
| Mgi Id | MGI:5635769 | Doi | 10.1523/JNEUROSCI.2888-13.2014 |
| Citation | Won L, et al. (2014) Striatal cholinergic cell ablation attenuates L-DOPA induced dyskinesia in Parkinsonian mice. J Neurosci 34(8):3090-4 |
| abstractText | 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. |
