4.6 Article

Striatal Activation by Optogenetics Induces Dyskinesias in the 6-Hydroxydopamine Rat Model of Parkinson Disease

Journal

MOVEMENT DISORDERS
Volume 32, Issue 4, Pages 530-537

Publisher

WILEY
DOI: 10.1002/mds.26947

Keywords

dyskinesias; optogenetics; Parkinson disease; medium spiny neurons; L-dopa

Funding

  1. Fundacion Gangoiti
  2. Marie Slodowksa-Curie Fellowship MSC-IF
  3. Spanish government [SAF2015-67239-P]
  4. CIBERNED [CB06/05/0055]
  5. SECITI from Mexico [037-2016]
  6. [ISCIII: SAF2016-78207-R]

Ask authors/readers for more resources

Background: Long-term levodopa (l-dopa) treatment is associated with the development of l-dopa-induced dyskinesias in the majority of patients with Parkinson disease (PD). The etiopathogonesis and mechanisms underlying l-dopa-induced dyskinesias are not well understood. Methods: We used striatal optogenetic stimulation to induce dyskinesias in a hemiparkinsonian model of PD in rats. Striatal dopamine depletion was induced unilaterally by 6-hydroxydopamine injection into the medial forebrain bundle. For the optogenetic manipulation, we injected adeno-associated virus particles expressing channelrhodopsin to stimulate striatal medium spiny neurons with a laser source. Results: Simultaneous optical activation of medium spiny neurons of the direct and indirect striatal pathways in the 6-hydroxydopamine lesion but l-dopa naive rats induced involuntary movements similar to l-dopa-induced dyskinesias, labeled here as optodyskinesias. Noticeably, optodyskinesias were facilitated by l-dopa in animals that did not respond initially to the laser stimulation. In general, optodyskinesias lasted while the laser stimulus was applied, but in some instances remained ongoing for a few seconds after the laser was off. Postmortem tissue analysis revealed increased FosB expression, a molecular marker of l-dopa-induced dyskinesias, primarily in medium spiny neurons of the direct pathway in the dopamine-depleted hemisphere. Conclusion: Selective optogenetic activation of the dorsolateral striatum elicits dyskinesias in the 6-hydroxydopamine rat model of PD. This effect was associated with a preferential activation of the direct striato-nigral pathway. These results potentially open new avenues in the understanding of mechanisms involved in l-dopa-induced dyskinesias. (c) 2017 International Parkinson and Movement Disorder Society

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available