TY - JOUR
T1 - Altered Motor Performance, Sleep EEG, and Parkinson’s Disease Pathology Induced by Chronic Sleep Deprivation in Lrrk2 G2019S Mice
AU - Liu, Xinyao
AU - Yu, Hang
AU - Wang, Yuanyuan
AU - Li, Song
AU - Cheng, Cheng
AU - Al-Nusaif, Murad
AU - Le, Weidong
N1 - Funding Information:
We thank Liaoning Provincial Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, and Dalian Medical University for the research infrastructure and support. This work was supported by the National Natural Science Foundation of China (81771521).
Funding Information:
We thank Liaoning Provincial Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, and Dalian Medical University for the research infrastructure and support. This work was supported by the National Natural Science Foundation of China (81771521).
Publisher Copyright:
© 2022, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.
PY - 2022/10
Y1 - 2022/10
N2 - Parkinson’s disease (PD) is a multifaceted disease in which environmental variables combined with genetic predisposition cause dopaminergic (DAergic) neuron loss in the substantia nigra pars compacta. The mutation of leucine-rich repeat kinase 2 (Lrrk2) is the most common autosomal dominant mutation in PD, and it has also been reported in sporadic cases. A growing body of research suggests that circadian rhythm disruption, particularly sleep-wake abnormality, is common during the early phase of PD. Our present study aimed to evaluate the impact of sleep deprivation (SD) on motor ability, sleep performance, and PD pathologies in Lrrk2G2019S transgenic mice. After two months of SD, Lrrk2G2019S mice at 12 months of age showed an exacerbated PD-like phenotype with motor deficits, a reduced striatal DA level, degenerated DAergic neurons, and altered sleep structure and biological rhythm accompanied by the decreased protein expression level of circadian locomotor output cycles kaput Lrrk2 gene in the brain. All these changes persisted and were even more evident in 18-month-old mice after 6 months of follow-up. Moreover, a significant increase in α-synuclein aggregation was found in SD-treated transgenic mice at 18 months of age. Taken together, our findings indicate that sleep abnormalities, as a risk factor, may contribute to the pathogenesis and progression of PD. Early detection of sleep disorders and improvement of sleep quality may help to delay disease progression and provide long-term clinical benefits.
AB - Parkinson’s disease (PD) is a multifaceted disease in which environmental variables combined with genetic predisposition cause dopaminergic (DAergic) neuron loss in the substantia nigra pars compacta. The mutation of leucine-rich repeat kinase 2 (Lrrk2) is the most common autosomal dominant mutation in PD, and it has also been reported in sporadic cases. A growing body of research suggests that circadian rhythm disruption, particularly sleep-wake abnormality, is common during the early phase of PD. Our present study aimed to evaluate the impact of sleep deprivation (SD) on motor ability, sleep performance, and PD pathologies in Lrrk2G2019S transgenic mice. After two months of SD, Lrrk2G2019S mice at 12 months of age showed an exacerbated PD-like phenotype with motor deficits, a reduced striatal DA level, degenerated DAergic neurons, and altered sleep structure and biological rhythm accompanied by the decreased protein expression level of circadian locomotor output cycles kaput Lrrk2 gene in the brain. All these changes persisted and were even more evident in 18-month-old mice after 6 months of follow-up. Moreover, a significant increase in α-synuclein aggregation was found in SD-treated transgenic mice at 18 months of age. Taken together, our findings indicate that sleep abnormalities, as a risk factor, may contribute to the pathogenesis and progression of PD. Early detection of sleep disorders and improvement of sleep quality may help to delay disease progression and provide long-term clinical benefits.
KW - Electroencephalogram
KW - Lrrk2 mutation
KW - Neurodegeneration
KW - Parkinson’s disease
KW - Sleep disturbance
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U2 - 10.1007/s12264-022-00881-2
DO - 10.1007/s12264-022-00881-2
M3 - Article
C2 - 35612787
AN - SCOPUS:85130762711
VL - 38
SP - 1170
EP - 1182
JO - Neuroscience Bulletin
JF - Neuroscience Bulletin
SN - 1673-7067
IS - 10
ER -