title: Evidence of an association between sleep and levodopa-induced dyskinesia in an animal model of Parkinson's disease.
abstract: Levodopa-induced dyskinesia (LID) represents a major challenge for clinicians treating patients affected by Parkinson's disease (PD). Although levodopa is the most effective treatment for PD, the remodeling effects induced by disease progression and the pharmacologic treatment itself cause a narrowing of the therapeutic window because of the development of LID. Although animal models of PD provide strong evidence that striatal plasticity underlies the development of dyskinetic movements, the pathogenesis of LID is not entirely understood. In recent years, slow homeostatic adjustment of intrinsic excitability occurring during sleep has been considered fundamental for network stabilization by gradually modifying plasticity thresholds. So far, how sleep affects on LID has not been investigated. Therefore, we measured synaptic downscaling across sleep episodes in a parkinsonian animal model showing dyskinetic movements similar to LID. Our electrophysiological, molecular, and behavioral results are consistent with an impaired synaptic homeostasis during sleep in animals showing dyskinesia. Accordingly, sleep deprivation causes an anticipation and worsening of LID supporting a link between sleep and the development of LID.
authors.affiliation: Experimental Laboratory, Neurocenter of Southern Switzerland, Lugano, Switzerland. Electronic address: salvatore.galati@eoc.ch.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galati
authors.affiliation: Experimental Laboratory, Neurocenter of Southern Switzerland, Lugano, Switzerland.
authors.forename: Agnese
authors.initials: A
authors.lastname: Salvadè
authors.affiliation: Department of Neurology, University of Berne, Berne, Switzerland.
authors.forename: Marta
authors.initials: M
authors.lastname: Pace
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Sarasso
authors.affiliation: Department of Neurology, University of Berne, Berne, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baracchi
authors.affiliation: Experimental Laboratory, Neurocenter of Southern Switzerland, Lugano, Switzerland; Department of Neurology, University of Berne, Berne, Switzerland.
authors.forename: Claudio L
authors.initials: CL
authors.lastname: Bassetti
authors.affiliation: Experimental Laboratory, Neurocenter of Southern Switzerland, Lugano, Switzerland; Department of Neurology, University of Berne, Berne, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Kaelin-Lang
authors.affiliation: Experimental Laboratory, Neurocenter of Southern Switzerland, Lugano, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Städler
authors.affiliation: Department of Neurology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Stanzione
authors.affiliation: Experimental Laboratory, Neurocenter of Southern Switzerland, Lugano, Switzerland; Parkinson Center, Center for Neurological Rehabilitation, Zihlschlacht, Switzerland.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Möller
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D006706:Homeostasis; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D010300:Parkinson Disease / Q000188:drug therapy*; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000150:complications
chemical_list: D007980:Levodopa
keywords: Levodopa-induced dyskinesia; Parkinson's disease; Sleep; Slow-wave activity; Synaptic homeostasis