論文

国際誌
2022年4月

Contribution of astrocytic histamine N-methyltransferase to histamine clearance and brain function in mice

Neuropharmacology
  • Rina Otsuka
  • Fumito Naganuma
  • Tadaho Nakamura
  • Hideki Miwa
  • Rumi Nakayama-Naono
  • Takuro Matsuzawa
  • Yurika Komatsu
  • Yuki Sato
  • Yuna Takahashi
  • Haruna Tatsuoka-Kitano
  • Kazuhiko Yanai
  • Takeo Yoshikawa
  • 全て表示

212
開始ページ
109065
終了ページ
109065
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.neuropharm.2022.109065
出版者・発行元
Elsevier BV

Brain histamine acts as a neurotransmitter in the regulation of various brain activities. Previous studies have shown that histamine N-methyltransferase (HNMT), a histamine-metabolizing enzyme, controls brain histamine concentration and brain function. However, the relative contribution of astrocytic or neuronal HNMT to the regulation of the histaminergic system is still inconclusive. Here, we phenotyped astrocytes-specific HNMT knockout (cKO) mice to clarify the involvement of astrocytic HNMT in histamine clearance and brain function. First, we performed histological examinations using HNMT reporter mice and showed a wide distribution of HNMT in the brain and astrocytic HNMT expression. Then, we created cKO mice by Cre-loxP system and confirmed that HNMT expression in cKO primary astrocytes was robustly decreased. Although total HNMT level in the cortex was not substantially different between control and cKO brains, histamine concentration after histamine release was elevated in cKO cortex. In behavioral tests, impaired motor coordination and lower locomotor activity were observed in the cKO mice. However, anxiety-like behaviors, depression-like behaviors, and memory functions were not altered by astrocytic HNMT disruption. Although sleep analysis demonstrated that the quantity of wakefulness and sleep did not change, the increased power density of delta frequency during wakefulness indicated lower cortical activation in cKO mice. These results demonstrate that astrocytic HNMT contributes to histamine clearance after histamine release in the cortex and plays a role in the regulation of motor coordination, locomotor activity, and vigilance state.

リンク情報
DOI
https://doi.org/10.1016/j.neuropharm.2022.109065
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35487272
ID情報
  • DOI : 10.1016/j.neuropharm.2022.109065
  • ISSN : 0028-3908
  • PubMed ID : 35487272

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