2023 Fiscal Year Research-status Report
Optical analysis of the heat production mechanism in the brain and its metabolic function in mammalian hibernation.
| Project/Area Number |
23KF0096
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| Research Institution | National Institutes of Natural Sciences |
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Principal Investigator |
根本 知己 大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 教授 (50291084)
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| Co-Investigator(Kenkyū-buntansha) |
CHANG CHING-PU 大学共同利用機関法人自然科学研究機構(機構直轄研究施設), 生命創成探究センター, 外国人特別研究員
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| Project Period (FY) |
2023-04-25 – 2025-03-31
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| Keywords | UCP1 thermo-regulation / mammalian hibernation / Thermal imaging |
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| Outline of Annual Research Achievements |
To address the role of UCP1 in the brain, we first confirmed the expression of UCP1 in the hypothalamus in the hamster, but not in the mouse, using multiple immunohistochemical techniques. We next performed quantitative analysis to characterize the expression of brain UCP1 during the hibernation cycle. We found that hypothalamic UCP1 expression was upregulated upon to the long-term 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. It suggested that there is a BAT independent thermoregulatory mechanism in the brain. Moreover, we established the virus injection techniques and optimized the acute slice calcium imaging procedure in the hamster brain, during which we preliminarily found that both astrocytes and neurons in the hypothalamus respond to the cold stimulation. We also confirmed the expression of the genetically encoded temperature indicator (GETI) B-gTEMP in the hamster brain, in which will be used to investigate the thermogenic capabilities of hypothalamic astrocytes and neurons. To specify the necessity of UCP1, all the experiments above will be conducted in wild-type and UCP1 knockout (KO) hamsters
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We found hypothalamic UCP1 expression was upregulated during long-term 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. We also found that both hypothalamic astrocytes and neurons respond to the cold stimulation. All techniques such as thermal imaging system have been established, and future works will be performed smoothly.
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| Strategy for Future Research Activity |
Our next step is to directly measure the temperature from the hypothalamus in Syrian hamsters with B-gTEMP using acute brain slice imaging under multiphoton microscopy at temperatures between 5 and 35 degrees. To exclusively examine the contribution of UCP1 in brain thermogenesis, we will either inactivate or knockdown the UCP1 during the acute brain slices thermal imaging.
To further understand the role of UCP1 in real hibernation conditions, we will first perform in vivo fibre photometry recording from hypothalamus expressing B-gTEMP to real-time trace the brain temperature during hibernation cycles. The in vivo recording will then be done in the UCP1-KO hamster to observe if KO of UCP1 disturbs brain thermogenesis.
As the previous papers have suggested that hibernators switch over to lipid-based metabolism in the brain to adapt to prolonged periods of starvation during hibernation, our results of the increased UCP1 in the pre-hibernation may be caused by the metabolic altering. To test our hypothesis, we will use Miniscope to access hypothalamic UCP1 function with B-gTEMP by altering the lipid metabolism in the brain.
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| Causes of Carryover |
Progress in research and rising prices made it difficult to purchase the originally planned items. We plan to purchase and use the necessary items for experiments by combining them with those for the next fiscal year. In addition, travel expenses for the presentation of new research results will be used systematically. In addition, since the next fiscal year is the final year of the project, all executions are scheduled to be completed.
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