共同研究報告書


研究区分 一般研究

研究課題

 哺乳類冬眠中の脳内熱産生メカニズムの光学的解析
新規・継続の別 継続（R05年度から）
研究代表者／所属 自然科学研究機構生命創成探究センター
研究代表者／職名 特任研究員
研究代表者／氏名 CHANG Ching Pu

研究分担者／氏名／所属／職名
　
氏　　名
所　　属
職　　名

1

 榎木亮介 自然科学研究機構生命創成探究センター Associate Professor

2

 LEE Ming Liang 自然科学研究機構生命創成探究センター Assistant Professor

3

 山口良文 北大低温研

研究目的 Hibernators use the strategy to survive harsh environments， such as low temperature and food scarcity， by reducing metabolism and body temperature. Body temperature is mainly controlled by brown adipose tissue (BAT) that is rich in mitochondria and highly expresses uncoupling protein 1 (UCP1)， where heat is generated. I found that UCP1 is also expressed in the hamster brain. However， it is unclear whether the brain UCP1 is functional. We will measure the intracellular temperature and study the role of brain UCP1 in the thermoregulation and the physiological functions during hibernation.
　　
研究内容・成果 We’ve confirmed the expression of UCP1 in neurons in the paraventricular nucleus of the hypothalamus (PVN) and in astrocytes near the third ventricle， which is innervated by tanycytes， in hamster， but not in mouse， with immunohistochemical staining. To verify the reliability of staining results， we examined brain samples from UCP1-KO hamsters to validate antibody specificity. However， the identical staining patterns were found， raising concerns about non-specific antibody binding. To bypass the use of antibodies， we then performed proteomics analysis to further validate the expression of UCP1 in hamster brain; nevertheless， the results were controversial as no major proteins have been detected. In parallel， we quantitatively analysis the RNA expression of brain UCP1 and found that hypothalamic UCP1 expression upregulated during the chronic cold exposure and returned to the same level as that of warm control during the deep torpor， whereas the amount of BAT UCP1 peaked during the deep torpor. However， the further RNA sequencing experiment did not fully support the finding as very low UCP1 RNA were detected. In summary， we could not conclude yet neither there is truly UCP1 expressed in the hamster brain nor the low expression of brain UCP1 could contribute to the thermoregulation.
Moving forward， we plan to continue efforts such as local temperature measurements in the hamster brain， while considering the possibility that brain thermogenesis may occur through mechanisms other than UCP1.
　　
成果となる論文・学会発表等 1. LEE ML， CHANG CP， TODA C， NEMOTO T， ENOKI R. Body temperature regulates glucose metabolism and torpid behavior. Nat Commun. 2025 Jul 10;16(1):6278. doi: 10.1038/s41467-025-61499-2. PMID: 40640117; PMCID: PMC12246491.
2. CP CHANG， ML LEE， T. NEMOTO， R. ENOKI. Visualizing Sensory Processing in Synthetic Hibernation. Invited presentation， 2025/11， 極限環境適応2025
3. CP CHANG， ML LEE， T. NEMOTO， R. ENOKI. In vivo two-photon calcium imaging of cortical activity during a hibernation-like state in mice. Poster， 2024/07， 7th International Hibernation Symposium
4. CP CHANG， ML LEE， T. NEMOTO， R. ENOKI. In vivo two-photon calcium imaging of cortical activity during a hibernation-like state in mice. Poster， 2024/06， FENS Forum 2024
5. R. Enoki， N. Kon， K. Shimizu， K. Kobayashi， S. Hiro， Ching-Pu Chang， et al. Cold-induced Suspension and Resetting of Ca2+ and Transcriptional Rhythms in the Suprachiasmatic Nucleus Neurons. iScience 26， 108390， December 15， 2023