Histamine N-methyltransferase regulates aggression and the sleep-wake cycle.
Histamine N-methyltransferase regulates aggression and the sleep-wake cycle.
复制标题
DOI：
10.1038/s41598-017-16019-8
复制
发表时间：
2017-11-21
影响因子：
4.6
通讯作者：
Yanai K
中科院分区：
文献类型：
--
作者：
Naganuma F;Nakamura T;Yoshikawa T;Iida T;Miura Y;Kárpáti A;Matsuzawa T;Yanai A;Mogi A;Mochizuki T;Okamura N;Yanai K
组胺是一种神经递质，调节包括睡眠-觉醒周期在内的多种生理功能。最近的研究报道，脑中的组胺能功能障碍与神经精神疾病有关。组胺N-甲基转移酶（HNMT）是一种在中枢神经系统中表达的酶，特异性代谢组胺;然而，HNMT的确切生理作用尚不清楚。因此，我们对Hnmt敲除小鼠（KO）进行表型分析，以确定HNMT与各种脑功能的相关性。首先，我们发现，HNMT缺乏增强脑组胺浓度，证实了HNMT在组胺失活中的作用。接下来，我们进行了全面的行为测试，并确定KO小鼠在居民入侵者和攻击性咬人行为测试中表现出高度攻击性行为。高侵略性KO小鼠的治疗与zolantidine，组胺H2受体（H2 R）拮抗剂，表明异常H2 R激活促进攻击KO小鼠的抑制。睡眠分析显示，KO小鼠在光照（非活动）期间表现出长时间的觉醒，在黑暗（活动）期间表现出代偿性睡眠。异常的睡眠行为被抑制的吡拉明，一种H1 R拮抗剂，在光周期之前，这表明过度的H1 R激活导致KO小鼠的睡眠-觉醒周期失调。这些观察为HNMT的生理作用提供了信息。
Histamine is a neurotransmitter that regulates diverse physiological functions including the sleep-wake cycle. Recent studies have reported that histaminergic dysfunction in the brain is associated with neuropsychiatric disorders. Histamine N-methyltransferase (HNMT) is an enzyme expressed in the central nervous system that specifically metabolises histamine; yet, the exact physiological roles of HNMT are unknown. Accordingly, we phenotyped Hnmt knockout mice (KO) to determine the relevance of HNMT to various brain functions. First, we showed that HNMT deficiency enhanced brain histamine concentrations, confirming a role for HNMT in histamine inactivation. Next, we performed comprehensive behavioural testing and determined that KO mice exhibited high aggressive behaviours in the resident-intruder and aggressive biting behaviour tests. High aggression in KO mice was suppressed by treatment with zolantidine, a histamine H2 receptor (H2R) antagonist, indicating that abnormal H2R activation promoted aggression in KO mice. A sleep analysis revealed that KO mice exhibited prolonged bouts of awakening during the light (inactive) period and compensatory sleep during the dark (active) period. Abnormal sleep behaviour was suppressed by treatment with pyrilamine, a H1R antagonist, prior to light period, suggesting that excessive H1R activation led to the dysregulation of sleep-wake cycles in KO mice. These observations inform the physiological roles of HNMT.
登录
查看更多内容
影响因子：
3.6
作者：
Mondillo, C;Patrignani, Z;Pignataro, O
通讯作者：
Pignataro, O
影响因子：
3.7
作者：
Ding Y;Yang Y;Yang X;Zhang T;Qiu X;He X;Wang W;Wang L;Sui H
通讯作者：
Sui H
影响因子：
64.8
作者：
Funato H;Miyoshi C;Fujiyama T;Kanda T;Sato M;Wang Z;Ma J;Nakane S;Tomita J;Ikkyu A;Kakizaki M;Hotta-Hirashima N;Kanno S;Komiya H;Asano F;Honda T;Kim SJ;Harano K;Muramoto H;Yonezawa T;Mizuno S;Miyazaki S;Connor L;Kumar V;Miura I;Suzuki T;Watanabe A;Abe M;Sugiyama F;Takahashi S;Sakimura K;Hayashi Y;Liu Q;Kume K;Wakana S;Takahashi JS;Yanagisawa M
通讯作者：
Yanagisawa M
组胺 H1 受体敲除小鼠的睡眠-觉醒特征发生改变，且对 H3 受体拮抗剂缺乏唤醒反应。
DOI：
10.1073/pnas.0600451103
发表时间：
2006-03-21
影响因子：
11.1
作者：
Huang, ZL;Mochizuki, T;Hayaishi, O
通讯作者：
Hayaishi, O
影响因子：
4.1
作者：
Jorgensen, Emilie A.;Vogelsang, Thomas W.;Kjaer, Andreas
通讯作者：
Kjaer, Andreas