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.
|Titolo:||Evidence of an association between sleep and levodopa-induced dyskinesia in an animal model of Parkinson's disease|
|Parole Chiave:||levodopa-induced dyskinesia; Parkinson's disease; sleep; slow-wave activity; synaptic homeostasis; neurology (clinical); neuroscience (all); aging; developmental biology; geriatrics and gerontology|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||mar-2015|
|Digital Object Identifier (DOI):||10.1016/j.neurobiolaging.2014.12.018|
|Appare nelle tipologie:||01 - Articolo su periodico|