Differential involvement of Ras-GRF1 and Ras-GRF2 in L-DOPA-induced dyskinesia.

ABSTRACT:

Objective

Recent findings have shown that pharmacogenetic manipulations of the Ras-ERK pathway provide a therapeutic means to tackle l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID). First, we investigated whether a prolonged l-DOPA treatment differentially affected ERK signaling in medium spiny neurons of the direct pathway (dMSNs) and in cholinergic aspiny interneurons (ChIs) and assessed the role of Ras-GRF1 in both subpopulations. Second, using viral-assisted technology, we probed Ras-GRF1 and Ras-GRF2 as potential targets in this pathway. We investigated how selective blockade of striatal Ras-GRF1 or Ras-GRF2 expression impacted on LID (induction, maintenance, and reversion) and its neurochemical correlates.

Methods

We used both Ras-GRF1 knockout mice and

SUBMITTER: Bido S 

PROVIDER: S-EPMC4479526 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature