2026-03-13T14:40:36Z https://hiroshima.repo.nii.ac.jp/oai

oai:hiroshima.repo.nii.ac.jp:02006380 2025-10-27T01:31:31Z 1730444907710

Histidine-containing dipeptide deficiency links to hyperactivity and depression-like behaviors in old female mice Braga, Jason D. Komaru, Takumi Umino, Mitsuki Nagao, Tomoka Matsubara, Kiminori Egusa, Ai Yanaka, Noriyuki Nishimura, Toshihide Kumrungsee, Thanutchaporn Homocarnosine GABA Hyperactivity Anxiety Depression CARNS1 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. 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.). http://purl.org/coar/resource_type/c_6501 Elsevier 2024-07-05 AM Biochemical and Biophysical Research Communications 150361 729 https://hiroshima.repo.nii.ac.jp/records/2006380 eng https://doi.org/10.1016/j.bbrc.2024.150361 open access © 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。