TY - JOUR
T1 - Evidence of an association between sleep and levodopa-induced dyskinesia in an animal model of Parkinson's disease
AU - Galati, Salvatore
AU - Salvadè, Agnese
AU - Pace, Marta
AU - Sarasso, Simone
AU - Baracchi, Francesca
AU - Bassetti, Claudio L.
AU - Kaelin-Lang, Alain
AU - Städler, Claudio
AU - Stanzione, Paolo
AU - Möller, Jens C.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - Levodopa-induced dyskinesia
KW - Parkinson's disease
KW - Sleep
KW - Slow-wave activity
KW - Synaptic homeostasis
UR - http://www.scopus.com/inward/record.url?scp=84923599452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923599452&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2014.12.018
DO - 10.1016/j.neurobiolaging.2014.12.018
M3 - Article
C2 - 25596726
AN - SCOPUS:84923599452
VL - 36
SP - 1577
EP - 1589
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 3
ER -