Archival ReportL-DOPA Treatment Selectively Restores Spine Density in Dopamine Receptor D2–Expressing Projection Neurons in Dyskinetic Mice
Section snippets
Methods and Materials
This study was carried out in 3–4-month-old male C57BL6 wild-type (WT) and bacterial artificial chromosome (BAC)-transgenic mice (D1R-tomato or D2R–enhanced green fluorescent protein [eGFP]). Animals were housed and maintained following the guidelines from European Union Council Directive (86/609/European Economic Community). Mice received an intrastriatal 6-OHDA (Sigma-Aldrich, Madrid, Spain) injection (parkinsonian group) or vehicle (sham group), as described previously (26). The mice
Induction of Dyskinesias in 6-OHDA-Lesioned Mice
To quantify L-DOPA-induced dyskinesias in parkinsonian WT, D1R-tomato, or D2R-eGFP mice, we scored orofacial, limb, and locomotive dyskinesia 30 min after L-DOPA or saline injection as previously described 14, 16, 26. After L-DOPA, parkinsonian BAC-transgenic mice developed marked dyskinetic movements affecting the contralateral forelimb and orofacial structures, together with trunk dystonia, similar to those observed in WT mice (Figure 1A). These symptoms were not observed in the saline group.
Discussion
Here we show that 6-OHDA lesions in the striatum reduce spine density in D1R-positive and D2R-positive MSN of D1R-tomato and D2R-eGFP BAC-transgenic mice. This reduction was similar to that observed in unidentified MSN in WT C57BL6 mice. We further show that these changes are restricted to totally denervated striatal areas. A major finding of the present study is that chronic L-DOPA, at doses inducing dyskinesia, reverses dendritic spine loss selectively in striatal MSNs expressing the D2R.
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