Histamine H1 receptor on astrocytes and neurons controls distinct aspects of mouse behaviour
Histamine H1 receptor on astrocytes and neurons controls distinct aspects of mouse behaviour
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DOI：
10.1038/s41598-019-52623-6
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发表时间：
2019-11-11
影响因子：
4.6
通讯作者：
Yanai, Kazuhiko
中科院分区：
文献类型：
--
作者：
Karpati, Aniko;Yoshikawa, Takeo;Yanai, Kazuhiko
组胺是一种重要的神经递质，有助于各种过程，包括睡眠-觉醒周期，学习，记忆和应激反应。其作用通过组胺H-1-H-4受体介导。基因敲除和药理学研究已经揭示了H-1受体在学习和记忆、攻击性调节和觉醒中的重要性。H-1受体在神经元和星形胶质细胞上大量表达。然而，迄今为止，研究选择性调查的神经元和星形胶质细胞H-1受体在行为中的作用是缺乏的。我们产生了新的星形胶质细胞和神经元特异性条件性敲除（cKO）小鼠，以解决这一知识缺口。cKO小鼠显示H-1受体基因表达的细胞特异性降低。行为评估显示了显着的变化，并强调了H-1受体对星形胶质细胞和神经元的重要性。两种细胞类型上的H-1受体在焦虑中起着重要作用。星形胶质细胞H-1受体参与调节攻击行为、昼夜节律和觉醒质量，但不参与睡眠行为。我们的研究结果强调了神经元H-1受体在识别记忆中的作用。总之，这项研究突出了星形胶质细胞和神经元上的H-1受体在各种脑功能中的新作用。
Histamine is an important neurotransmitter that contributes to various processes, including the sleep-wake cycle, learning, memory, and stress responses. Its actions are mediated through histamine H-1-H-4 receptors. Gene knockout and pharmacological studies have revealed the importance of H-1 receptors in learning and memory, regulation of aggression, and wakefulness. H-1 receptors are abundantly expressed on neurons and astrocytes. However, to date, studies selectively investigating the roles of neuronal and astrocytic H-1 receptors in behaviour are lacking. We generated novel astrocyte- and neuron-specific conditional knockout (cKO) mice to address this gap in knowledge. cKO mice showed cell-specific reduction of H-1 receptor gene expression. Behavioural assessment revealed significant changes and highlighted the importance of H-1 receptors on both astrocytes and neurons. H-1 receptors on both cell types played a significant role in anxiety. Astrocytic H-1 receptors were involved in regulating aggressive behaviour, circadian rhythms, and quality of wakefulness, but not sleep behaviour. Our results emphasise the roles of neuronal H-1 receptors in recognition memory. In conclusion, this study highlights the novel roles of H-1 receptors on astrocytes and neurons in various brain functions.