Striatal RGS4 levels were modulated by DA depletion and L-Dopa
treatment
To investigate whether RGS4 inhibition corrects a plastic adaptation of
RGS4 occurring as a consequence of DA depletion and/or L-Dopa
administration (Geurts et al. ,
2003; Ko et al. , 2014), RGS4
levels were measured by Western analysis in the striatum of naïve,
L-Dopa naïve 6-OHDA hemilesioned and dyskinetic rats (Fig. 8). In
dyskinetic rats, RGS4 levels were measured both ON and OFF L-Dopa. The
specificity of the antibody used was first confirmed in RGS4 knockout
mice (Supp Fig. 1). ANOVA revealed a strong effect of treatment
(F7,46=7.95). A marked decrease in RGS4 protein levels
was found in both the lesioned (-64%) and unlesioned (-51%) striatum
of 6-OHDA animals, when compared with respective naïve counterparts
(Fig. 8A). If RGS4 levels were expressed as lesioned-to-unlesioned
ratio, a significant reduction was detected in 6-OHDA hemilesioned rats
compared to naive rats (H3,20=13.73) (Fig.8B). Chronic
L-Dopa (OFF group) normalized the ratio. However, acute L-Dopa (ON
group) reversed it, causing a 44% increase of RGS4 levels in the
lesioned striatum. This suggests that RGS4 is rapidly upregulated in the
lesioned striatum of dyskinetic animals following acute stimulation of
aberrant D1 receptor signaling by L-Dopa.