Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.
Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.
复制标题
DOI：
10.1371/journal.pone.0187888
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Kodama T
中科院分区：
文献类型：
--
作者：
Toyoda H;Honda Y;Tanaka S;Miyagawa T;Honda M;Honda K;Tokunaga K;Kodama T
发作性睡病是由下丘脑分泌素（Hcrt）神经元缺失引起的，与多种遗传和环境因素有关。尽管免疫异常被认为与发作性睡病的病因有关，但尚未建立起决定性的机制。趋化因子受体3（C-C motif receptor 3，CCR 3）是一种新的嗜睡症易感基因。为了了解CCR 3在发作性睡病发展中的作用，我们研究了Ccr 3敲除（KO）小鼠的睡眠-觉醒模式。Ccr 3 KO小鼠在亮相表现出片段化的睡眠模式，而在暗相的整体睡眠结构在Ccr 3 KO小鼠和野生型（WT）同窝仔之间没有差异。腹腔内注射脂多糖（LPS）促进觉醒和抑制REM和NREM睡眠在Ccr 3 KO和WT小鼠的轻相。相反，LPS抑制觉醒和促进NREM睡眠在黑暗阶段的两种基因型。LPS给药后，与WT小鼠相比，Ccr 3 KO小鼠在清醒期花费的时间比例较高，而在NREM睡眠期花费的时间比例较低。与WT小鼠相比，Ccr 3 KO小鼠中LPS诱导的睡眠模式变化更大。此外，我们定量了Hcrt神经元的数量，发现Ccr 3 KO小鼠与WT小鼠相比，外侧下丘脑中的Hcrt神经元较少。我们发现Ccr 3基因敲除小鼠在休息期的睡眠模式和Hcrt神经元数量异常。这些观察结果表明CCR 3在发作性睡病患者的睡眠-觉醒调节中的作用。
Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif) receptor 3 (CCR3) as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO) mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT) littermates. Intraperitoneal injection of lipopolysaccharide (LPS) promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.
登录
查看更多内容
影响因子：
5.2
作者：
Holm, Anja;Lin, Ling;Kornum, Birgitte R.
通讯作者：
Kornum, Birgitte R.
影响因子：
4.5
作者：
Faraco J;Lin L;Kornum BR;Kenny EE;Trynka G;Einen M;Rico TJ;Lichtner P;Dauvilliers Y;Arnulf I;Lecendreux M;Javidi S;Geisler P;Mayer G;Pizza F;Poli F;Plazzi G;Overeem S;Lammers GJ;Kemlink D;Sonka K;Nevsimalova S;Rouleau G;Desautels A;Montplaisir J;Frauscher B;Ehrmann L;Högl B;Jennum P;Bourgin P;Peraita-Adrados R;Iranzo A;Bassetti C;Chen WM;Concannon P;Thompson SD;Damotte V;Fontaine B;Breban M;Gieger C;Klopp N;Deloukas P;Wijmenga C;Hallmayer J;Onengut-Gumuscu S;Rich SS;Winkelmann J;Mignot E
通讯作者：
Mignot E
影响因子：
3.7
作者：
Calil IL;Zarpelon AC;Guerrero AT;Alves-Filho JC;Ferreira SH;Cunha FQ;Cunha TM;Verri WA Jr
通讯作者：
Verri WA Jr
影响因子：
15.1
作者：
Gaykema, Ronald P. A.;Goehler, Lisa E.
通讯作者：
Goehler, Lisa E.
影响因子：
30.8
作者：
Hallmayer, Joachim;Faraco, Juliette;Mignot, Emmanuel
通讯作者：
Mignot, Emmanuel