TY - JOUR
T1 - Histamine H1 receptor on astrocytes and neurons controls distinct aspects of mouse behaviour
AU - Kárpáti, Anikó
AU - Yoshikawa, Takeo
AU - Naganuma, Fumito
AU - Matsuzawa, Takuro
AU - Kitano, Haruna
AU - Yamada, Yo
AU - Yokoyama, Mariko
AU - Futatsugi, Akira
AU - Mikoshiba, Katsuhiko
AU - Yanai, Kazuhiko
N1 - Funding Information:
This work was supported by Grant-in-Aid for the Japan Society for the Promotion of Science (JSPS) fellows (18J11446) and by a Grant-in-Aid for Scientific Research (C) (18K06886), also from JSPS. We acknowledge the support of the Nishinomiya Basic Research Fund, Takeda Science Foundation, and the Tohoku University Division for Interdisciplinary Advanced Research and Education. We also acknowledge the technical support of the Biomedical Research Core of Tohoku University Graduate School of Medicine and the Biomedical Research Unit of Tohoku University Hospital.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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 H1–H4 receptors. Gene knockout and pharmacological studies have revealed the importance of H1 receptors in learning and memory, regulation of aggression, and wakefulness. H1 receptors are abundantly expressed on neurons and astrocytes. However, to date, studies selectively investigating the roles of neuronal and astrocytic H1 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 H1 receptor gene expression. Behavioural assessment revealed significant changes and highlighted the importance of H1 receptors on both astrocytes and neurons. H1 receptors on both cell types played a significant role in anxiety. Astrocytic H1 receptors were involved in regulating aggressive behaviour, circadian rhythms, and quality of wakefulness, but not sleep behaviour. Our results emphasise the roles of neuronal H1 receptors in recognition memory. In conclusion, this study highlights the novel roles of H1 receptors on astrocytes and neurons in various brain functions.
AB - 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 H1–H4 receptors. Gene knockout and pharmacological studies have revealed the importance of H1 receptors in learning and memory, regulation of aggression, and wakefulness. H1 receptors are abundantly expressed on neurons and astrocytes. However, to date, studies selectively investigating the roles of neuronal and astrocytic H1 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 H1 receptor gene expression. Behavioural assessment revealed significant changes and highlighted the importance of H1 receptors on both astrocytes and neurons. H1 receptors on both cell types played a significant role in anxiety. Astrocytic H1 receptors were involved in regulating aggressive behaviour, circadian rhythms, and quality of wakefulness, but not sleep behaviour. Our results emphasise the roles of neuronal H1 receptors in recognition memory. In conclusion, this study highlights the novel roles of H1 receptors on astrocytes and neurons in various brain functions.
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U2 - 10.1038/s41598-019-52623-6
DO - 10.1038/s41598-019-52623-6
M3 - Article
C2 - 31712580
AN - SCOPUS:85074871615
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 16451
ER -