LRRK2 Deficiency Aggravates Sleep Deprivation-Induced Cognitive Loss by Perturbing Synaptic Pruning in Mice.
LRRK2 Deficiency Aggravates Sleep Deprivation-Induced Cognitive Loss by Perturbing Synaptic Pruning in Mice.
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LRRK2 缺陷通过干扰小鼠突触修剪而加剧睡眠剥夺引起的认知丧失
DOI：
10.3390/brainsci12091200
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发表时间：
2022-09-06
期刊：
影响因子：
3.3
通讯作者：
Pan, Xiaodong
中科院分区：
文献类型：
--
作者：
Cheng, Xiaojuan;Wu, Xilin;Zhang, Yuying;Li, Weian;Feng, Linjuan;You, Hanlin;Yang, Siyu;Yang, Dongping;Chen, Xiaochun;Pan, Xiaodong
富含亮氨酸重复序列激酶2（LRRK 2）基因的突变与神经退行性疾病中明显的睡眠障碍或认知功能障碍相关。然而，LRRK 2缺乏对睡眠节律和睡眠剥夺相关的认知变化的影响，以及相关的潜在机制尚未揭示。在这项研究中，Lrrk 2-/-和Lrrk 2 +/+小鼠经历正常睡眠（S）或睡眠剥夺（SD）。采用睡眠记录、行为测试、Golgi-cox染色、免疫荧光和实时荧光PCR等方法评价LRRK 2缺陷对睡眠行为的影响并探讨其机制。结果显示，SD后，LRRK 2缺陷小鼠表现出NREM延长和REM缩短，并报告树突棘减少，小胶质细胞活化增加，前额叶皮层突触内吞作用增加。同时，SD后，LRRK 2缺陷加重了认知障碍，尤其是在恐惧条件反射提示的回忆记忆中。我们的研究结果表明，LRRK 2调节REM/NREM睡眠，其缺陷可能会通过扰乱小鼠的突触可塑性和小胶质细胞突触修剪来加剧睡眠剥夺相关的认知障碍。
Mutations of the leucine-rich repeat kinase 2 (LRRK2) gene are associated with pronounced sleep disorders or cognitive dysfunction in neurodegenerative diseases. However, the effects of LRRK2 deficiency on sleep rhythms and sleep deprivation-related cognitive changes, and the relevant underlying mechanism, remain unrevealed. In this study, Lrrk2-/- and Lrrk2+/+ mice were subjected to normal sleep (S) or sleep deprivation (SD). Sleep recording, behavioral testing, Golgi-cox staining, immunofluorescence, and real-time PCR were employed to evaluate the impacts of LRRK2 deficiency on sleep behaviors and to investigate the underlying mechanisms. The results showed that after SD, LRRK2-deficient mice displayed lengthened NREM and shortened REM, and reported decreased dendritic spines, increased microglial activation, and synaptic endocytosis in the prefrontal cortex. Meanwhile, after SD, LRRK2 deficiency aggravated cognitive impairments, especially in the recall memory cued by fear conditioning test. Our findings evidence that LRRK2 modulates REM/NREM sleep and its deficiency may exacerbate sleep deprivation-related cognitive disorders by perturbing synaptic plasticity and microglial synaptic pruning in mice.
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影响因子：
16.6
作者：
Liu H;Wang X;Chen L;Chen L;Tsirka SE;Ge S;Xiong Q
通讯作者：
Xiong Q
影响因子：
3.1
作者：
Nolan SO;Reynolds CD;Smith GD;Holley AJ;Escobar B;Chandler MA;Volquardsen M;Jefferson T;Pandian A;Smith T;Huebschman J;Lugo JN
通讯作者：
Lugo JN
DOI：
10.18632/aging.202591
发表时间：
2021-02-11
期刊：
Aging
影响因子：
--
作者：
Robbins R;Quan SF;Weaver MD;Bormes G;Barger LK;Czeisler CA
通讯作者：
Czeisler CA
影响因子：
4.6
作者：
Purple RJ;Sakurai T;Sakaguchi M
通讯作者：
Sakaguchi M
影响因子：
8.6
作者：
Srivatsal, Sindhu;Cholerton, Brenna;Leverenz, James B.;Wszolek, Zbigniew K.;Uitti, Ryan J.;Dickson, Dennis W.;Weintraub, Daniel;Trojanowski, John Q.;Van Deerlin, Vivianna M.;Quinn, Joseph F.;Chung, Kathryn A.;Peterson, Amie L.;Factor, Stewart A.;Wood-Siverio, Cathy;Goldman, Jennifer G.;Stebbins, Glenn T.;Bernard, Bryan;Ritz, Beate;Rausch, Rebecca;Espay, Alberto J.;Revilla, Fredy J.;Devoto, Johnna;Rosenthal, Liana S.;Dawson, Ted M.;Albert, Marilyn S.;Mata, Ignacio F.;Hu, Shu-Ching;Montine, Kathleen S.;Johnson, Catherine;Montine, Thomas J.;Edwards, Karen L.;Zhang, Jing;Zabetian, Cyrus P.
通讯作者：
Zabetian, Cyrus P.