Research Paper Volume 11, Issue 24 pp 12315—12327
β-arrestin2 alleviates L-dopa–induced dyskinesia via lower D1R activity in Parkinson’s rats
- 1 Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 2 Department of Neurology, Huzhou Central Hospital, Zhejiang, China
- 3 The center of Traditional Chinese Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
received: September 1, 2019 ; accepted: November 24, 2019 ; published: December 18, 2019 ;https://doi.org/10.18632/aging.102574
How to Cite
Copyright © 2019 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The cause of the L-dopa–induced dyskinesia (LID) has been ascribed to G-protein coupled receptor (GPCR) supersensitivity and uncontrolled downstream signaling. It is now supposed that β-arrestin2 affects GPCR signaling through its ability to scaffold various intracellular molecules. We used the rAAV (recombinant adeno-associated virus) vectors to overexpress and ablation of β-arrestin2. L-dopa-induced changes in expression of signaling molecules and other proteins in the striatum were examined by western blot and immunohistochemically. Our data demonstrated that via AAV-mediated overexpression of β-arrestin2 attenuated LID performance in 6-OHDA-lesioned rodent models. β-arrestin2 suppressed LID behavior without compromising the antiparkinsonian effects of L-dopa. Moreover, we also found that the anti-dyskinetic effect of β-arrestin2 was reversed by SKF38393, a D1R agonist. On the contrary, the rat knockdown study demonstrated that reduced availability of β-arrestin2 deteriorated LID performance, which was counteracted by SCH23390, a D1R antagonist. These data not only demonstrate a central role for β-arrestin2/GPCR signaling in LID, but also show the D1R signal pathway changes occurring in response to dopaminergic denervation and pulsatile administration of L-dopa.