Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 06 2022
09 06 2022
Historique:
received:
19
08
2021
accepted:
23
05
2022
entrez:
10
6
2022
pubmed:
11
6
2022
medline:
14
6
2022
Statut:
epublish
Résumé
Chronic Levodopa therapy, the gold-standard treatment for Parkinson's Disease (PD), leads to the emergence of involuntary movements, called levodopa-induced dyskinesia (LID). Cerebellar stimulation has been shown to decrease LID severity in PD patients. Here, in order to determine how cerebellar stimulation induces LID alleviation, we performed daily short trains of optogenetic stimulations of Purkinje cells (PC) in freely moving LID mice. We demonstrated that these stimulations are sufficient to suppress LID or even prevent their development. This symptomatic relief is accompanied by the normalization of aberrant neuronal discharge in the cerebellar nuclei, the motor cortex and the parafascicular thalamus. Inhibition of the cerebello-parafascicular pathway counteracted the beneficial effects of cerebellar stimulation. Moreover, cerebellar stimulation reversed plasticity in D1 striatal neurons and normalized the overexpression of FosB, a transcription factor causally linked to LID. These findings demonstrate LID alleviation and prevention by daily PC stimulations, which restore the function of a wide motor network, and may be valuable for LID treatment.
Identifiants
pubmed: 35680891
doi: 10.1038/s41467-022-30844-0
pii: 10.1038/s41467-022-30844-0
pmc: PMC9184492
doi:
Substances chimiques
Antiparkinson Agents
0
Levodopa
46627O600J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3211Informations de copyright
© 2022. The Author(s).
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