Histidine-containing dipeptide deficiency links to hyperactivity and depression-like behaviors in old female mice
Biochemical and Biophysical Research Communications 729 巻 150361 号
2024-07-05 発行
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| ファイル情報(添付) | |
| タイトル ( eng ) |
Histidine-containing dipeptide deficiency links to hyperactivity and depression-like behaviors in old female mice
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| 作成者 |
Braga Jason D.
Komaru Takumi
Umino Mitsuki
Nagao Tomoka
Matsubara Kiminori
Egusa Ai
Nishimura Toshihide
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| 収録物名 |
Biochemical and Biophysical Research Communications
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| 巻 | 729 |
| 号 | 150361 |
| 抄録 |
Carnosine, anserine, and homocarnosine are histidine-containing dipeptides (HCDs) abundant in the skeletal muscle and nervous system in mammals. To date, studies have extensively demonstrated effects of carnosine and anserine, the predominant muscular HCDs, on muscular functions and exercise performance. However, homocarnosine, the predominant brain HCD, is underexplored. Moreover, roles of homocarnosine and its related HCDs in the brain and behaviors remain poorly understood. Here, we investigated potential roles of endogenous brain homocarnosine and its related HCDs in behaviors by using carnosine synthase-1-deficient (Carns1−/−) mice. We found that old Carns1−/− mice (female 12 months old) exhibited hyperactivity- and depression-like behaviors with higher plasma corticosterone levels on light-dark transition and forced swimming tests, but had no defects in spontaneous locomotor activity, repetitive behavior, olfactory functions, and learning and memory abilities, as compared with their age-matched wild-type (WT) mice. We confirmed that homocarnosine and its related HCDs were deficient across brain areas of Carns1−/− mice. Homocarnosine deficiency exhibited small effects on its constituent γ-aminobutyric acid (GABA) in the brain, in which GABA levels in hypothalamus and olfactory bulb were higher in Carns1−/− mice than in WT mice. In WT mice, homocarnosine and GABA were highly present in hypothalamus, thalamus, and olfactory bulb, and their brain levels did not decrease in old mice when compared with younger mice (3 months old). Our present findings provide new insights into roles of homocarnosine and its related HCDs in behaviors and neurological disorders.
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| 著者キーワード |
Homocarnosine
GABA
Hyperactivity
Anxiety
Depression
CARNS1
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| 内容記述 |
This work was supported by Grant-in-Aid for Early Career Scientists (No. 21K14804 to T. K.) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT, Tokyo) and the 2021 Danone Institute of Japan Foundation (DIJF) Research Grant (Tokyo, Japan) (to T.K.).
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| 言語 |
英語
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| 資源タイプ | 学術雑誌論文 |
| 出版者 |
Elsevier
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| 発行日 | 2024-07-05 |
| 権利情報 |
© 2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
This is not the published version. Please cite only the published version.
この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。
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| 出版タイプ | Accepted Manuscript（出版雑誌の一論文として受付されたもの。内容とレイアウトは出版社の投稿様式に沿ったもの） |
| アクセス権 | エンバーゴ期間中 |
| 収録物識別子 |
[DOI] https://doi.org/10.1016/j.bbrc.2024.150361
～の異版である
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| 助成機関名 |
日本学術振興会
Japan Society for the Promotion of Science
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| 助成機関識別子 |
[Crossref Funder] https://doi.org/10.13039/501100001691
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| 研究課題名 |
カルノシンの骨格筋再生における生理的役割の解明、および応用
カルノシンの骨格筋再生における生理的役割の解明、および応用
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| 研究課題番号 |
21K14804
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| 備考 | The full-text file will be made open to the public on 5 July 2025 in accordance with publisher's 'Terms and Conditions for Self-Archiving' |
