TY - JOUR
T1 - Melatonin attenuates hLRRK2-induced Sleep disturbances and synaptic dysfunction in a Drosophila model of Parkinson's disease
AU - Sun, Xicui
AU - Ran, Dongzhi
AU - Zhao, Xiaofeng
AU - Huang, Yi
AU - Long, Simei
AU - Liang, Fengyin
AU - Guo, Wenyuan
AU - Nucifora, Frederick C.
AU - Gu, Huaiyu
AU - Lu, Xilin
AU - Chen, Ling
AU - Zeng, Jinsheng
AU - Ross, Christopher A.
AU - Pei, Zhong
N1 - Funding Information:
The current study was supported by grants from the National Natural Science Foundation of China (grant no. 81371255), the Doctoral Program of Higher Education of China (grant no. 20110171110058) and the Guangdong Province Science and Technology Department Project (grant nos. 2011B050400031 and 2012B031800107).
PY - 2016/5
Y1 - 2016/5
N2 - Sleep problems are the most common non-motor symptoms in Parkinson's disease (PD), and are more difficult to treat than the motor symptoms. In the current study, the role of human leucine-rich repeat kinase 2 (hLRRK2), the most common genetic cause of PD, was investigated with regards to sleep problems, and the therapeutic potential of melatonin in hLRRK2-associated sleep problems was explored in Drosophila. hLRRK2 was selectively expressed in the mushroom bodies (MBs) in Drosophila and sleep patterns were measured using the Drosophila Activity Monitoring System. MB expression of hLRRK2 resulted in sleep problems, presyn - aptic dysfunction as evidenced by reduced miniature excitatory postsynaptic current (mEPSC) and excitatory postsynaptic potential (EPSP) frequency, and excessive synaptic plasticity such as increased axon bouton density. Treatment with melatonin at 4 mM significantly attenuated the sleep problems and rescued the reduction in mEPSC and EPSP frequency in the hLRRK2 transgenic flies. The present study demonstrates that MB expression of hLRRK2 in flies recapitulates the clinical features of the sleep disturbances in PD, and that melatonin attenuates hLRRK2-induced sleep disorders and synaptic dysfunction, suggesting the therapeutic potential of melatonin in PD patients carrying LRRK2 mutations.
AB - Sleep problems are the most common non-motor symptoms in Parkinson's disease (PD), and are more difficult to treat than the motor symptoms. In the current study, the role of human leucine-rich repeat kinase 2 (hLRRK2), the most common genetic cause of PD, was investigated with regards to sleep problems, and the therapeutic potential of melatonin in hLRRK2-associated sleep problems was explored in Drosophila. hLRRK2 was selectively expressed in the mushroom bodies (MBs) in Drosophila and sleep patterns were measured using the Drosophila Activity Monitoring System. MB expression of hLRRK2 resulted in sleep problems, presyn - aptic dysfunction as evidenced by reduced miniature excitatory postsynaptic current (mEPSC) and excitatory postsynaptic potential (EPSP) frequency, and excessive synaptic plasticity such as increased axon bouton density. Treatment with melatonin at 4 mM significantly attenuated the sleep problems and rescued the reduction in mEPSC and EPSP frequency in the hLRRK2 transgenic flies. The present study demonstrates that MB expression of hLRRK2 in flies recapitulates the clinical features of the sleep disturbances in PD, and that melatonin attenuates hLRRK2-induced sleep disorders and synaptic dysfunction, suggesting the therapeutic potential of melatonin in PD patients carrying LRRK2 mutations.
KW - Drosophila
KW - Electrophysiology properties
KW - LRRK2
KW - Melatonin
KW - Mushroom body
KW - Sleep pattern
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UR - http://www.scopus.com/inward/citedby.url?scp=84964711891&partnerID=8YFLogxK
U2 - 10.3892/mmr.2016.4991
DO - 10.3892/mmr.2016.4991
M3 - Article
C2 - 26985725
AN - SCOPUS:84964711891
SN - 1791-2997
VL - 13
SP - 3936
EP - 3944
JO - Molecular Medicine Reports
JF - Molecular Medicine Reports
IS - 5
ER -