{"title":"组胺H1和H3受体在间歇性睡眠剥夺小鼠情绪调节中的作用。","authors":"Fukie Yaoita, Hiroki Imaizumi, Keigo Kawanami, Masahiro Tsuchiya, Koichi Tan-No","doi":"10.1248/bpb.b25-00028","DOIUrl":null,"url":null,"abstract":"<p><p>The central histamine system is involved in several physiological behaviors and neurological disorders, including the sleep-wake cycle, anxiety-related behaviors (both high and low anxiety), and attention deficit hyperactivity disorder (ADHD). Histamine is synthesized from l-histidine by histidine decarboxylase (HDC) and primarily metabolized by histamine-N-methyltransferase (HNMT) in the central nervous system. We previously reported that mice with intermittent sleep deprivation may exhibit impulsive-like symptoms resembling ADHD and low-anxiety behavior. However, the specific role of histaminergic systems in these behaviors remains unclear. In this study, we evaluated HDC expression levels in the hypothalamus as well as the expression of histamine H1 to H4 receptors and HNMT in the hypothalamus and frontal cortex of sleep-deprived mice. Moreover, the effects of administering histidine, a histamine precursor, and inhibitors of each histamine receptor on sleep deprivation-induced low-anxiety and impulsive-like behaviors were examined using an elevated plus maze test. The expressions of HDC and histamine H1 and H3 receptors in the hypothalamus increased, while that of histamine H1 receptors in the frontal cortex of sleep-deprived mice decreased. The low-anxiety and impulsive-like behaviors in intermittent sleep-deprived mice significantly decreased and increased, respectively, following the administration of histamine H1 and H3 receptor blockers and histidine. Collectively, these findings suggest that the low-anxiety behavior and impulsive-like ADHD symptoms induced by intermittent sleep deprivation may result from the overstimulation of histamine H1 and H3 receptors by elevated histamine, together with increased hypothalamic HDC expression. Furthermore, they suggest that sufficient sleep may contribute to ameliorating ADHD symptoms.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"545-554"},"PeriodicalIF":1.7000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Role of Histamine H1 and H3 Receptors in Emotion Regulation in Intermittent Sleep-Deprived Mice.\",\"authors\":\"Fukie Yaoita, Hiroki Imaizumi, Keigo Kawanami, Masahiro Tsuchiya, Koichi Tan-No\",\"doi\":\"10.1248/bpb.b25-00028\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The central histamine system is involved in several physiological behaviors and neurological disorders, including the sleep-wake cycle, anxiety-related behaviors (both high and low anxiety), and attention deficit hyperactivity disorder (ADHD). Histamine is synthesized from l-histidine by histidine decarboxylase (HDC) and primarily metabolized by histamine-N-methyltransferase (HNMT) in the central nervous system. We previously reported that mice with intermittent sleep deprivation may exhibit impulsive-like symptoms resembling ADHD and low-anxiety behavior. However, the specific role of histaminergic systems in these behaviors remains unclear. In this study, we evaluated HDC expression levels in the hypothalamus as well as the expression of histamine H1 to H4 receptors and HNMT in the hypothalamus and frontal cortex of sleep-deprived mice. Moreover, the effects of administering histidine, a histamine precursor, and inhibitors of each histamine receptor on sleep deprivation-induced low-anxiety and impulsive-like behaviors were examined using an elevated plus maze test. The expressions of HDC and histamine H1 and H3 receptors in the hypothalamus increased, while that of histamine H1 receptors in the frontal cortex of sleep-deprived mice decreased. The low-anxiety and impulsive-like behaviors in intermittent sleep-deprived mice significantly decreased and increased, respectively, following the administration of histamine H1 and H3 receptor blockers and histidine. Collectively, these findings suggest that the low-anxiety behavior and impulsive-like ADHD symptoms induced by intermittent sleep deprivation may result from the overstimulation of histamine H1 and H3 receptors by elevated histamine, together with increased hypothalamic HDC expression. 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引用次数: 0
摘要
中枢组胺系统参与多种生理行为和神经系统疾病,包括睡眠-觉醒周期、焦虑相关行为(高焦虑和低焦虑)和注意缺陷多动障碍(ADHD)。组胺是由l-组氨酸通过组氨酸脱羧酶(HDC)合成的,主要由中枢神经系统的组胺- n -甲基转移酶(HNMT)代谢。我们之前报道过间歇性睡眠剥夺的小鼠可能会表现出类似多动症和低焦虑行为的冲动性症状。然而,组胺能系统在这些行为中的具体作用尚不清楚。在本研究中,我们评估了睡眠剥夺小鼠下丘脑中HDC的表达水平,以及下丘脑和额叶皮层中组胺H1到H4受体和HNMT的表达。此外,使用升高+迷宫测试,研究了组氨酸(一种组胺前体)和组胺受体抑制剂对睡眠剥夺引起的低焦虑和冲动行为的影响。睡眠剥夺小鼠下丘脑HDC和组胺H1、H3受体表达增加,额叶皮层组胺H1受体表达减少。在给予组胺H1和H3受体阻滞剂和组氨酸后,间歇性睡眠剥夺小鼠的低焦虑和冲动行为分别显著减少和增加。综上所述,这些发现提示间歇性睡眠剥夺引起的低焦虑行为和冲动性样ADHD症状可能是由于组胺升高过度刺激组胺H1和H3受体,同时下丘脑HDC表达增加所致。此外,他们认为充足的睡眠可能有助于改善ADHD症状。
Role of Histamine H1 and H3 Receptors in Emotion Regulation in Intermittent Sleep-Deprived Mice.
The central histamine system is involved in several physiological behaviors and neurological disorders, including the sleep-wake cycle, anxiety-related behaviors (both high and low anxiety), and attention deficit hyperactivity disorder (ADHD). Histamine is synthesized from l-histidine by histidine decarboxylase (HDC) and primarily metabolized by histamine-N-methyltransferase (HNMT) in the central nervous system. We previously reported that mice with intermittent sleep deprivation may exhibit impulsive-like symptoms resembling ADHD and low-anxiety behavior. However, the specific role of histaminergic systems in these behaviors remains unclear. In this study, we evaluated HDC expression levels in the hypothalamus as well as the expression of histamine H1 to H4 receptors and HNMT in the hypothalamus and frontal cortex of sleep-deprived mice. Moreover, the effects of administering histidine, a histamine precursor, and inhibitors of each histamine receptor on sleep deprivation-induced low-anxiety and impulsive-like behaviors were examined using an elevated plus maze test. The expressions of HDC and histamine H1 and H3 receptors in the hypothalamus increased, while that of histamine H1 receptors in the frontal cortex of sleep-deprived mice decreased. The low-anxiety and impulsive-like behaviors in intermittent sleep-deprived mice significantly decreased and increased, respectively, following the administration of histamine H1 and H3 receptor blockers and histidine. Collectively, these findings suggest that the low-anxiety behavior and impulsive-like ADHD symptoms induced by intermittent sleep deprivation may result from the overstimulation of histamine H1 and H3 receptors by elevated histamine, together with increased hypothalamic HDC expression. Furthermore, they suggest that sufficient sleep may contribute to ameliorating ADHD symptoms.
期刊介绍:
Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012.
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