Mechanism of spontaneous oscillatory activity in medullary astrocytes involved in respiratory rhythm generation
Project/Area Number |
17K08559
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General physiology
|
Research Institution | National Hospital Organization Murayama Medical Center |
Principal Investigator |
Okada Yasumasa 独立行政法人国立病院機構村山医療センター(臨床研究部), 電気生理学研究室, 客員研究員 (80160688)
|
Project Period (FY) |
2017-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 呼吸中枢 / アストロサイト / グリア細胞 / カルシウムイメージング / 摘出脳幹脊髄標本 / 低酸素 / 低酸素換気応答 / 呼吸調節 / 呼吸リズム / 延髄 / 二酸化炭素換気応答 / ニューロン / 脳幹 / 呼吸リズム形成 / preBotzinger Complex / 生理学 / 解剖学 / 神経科学 / 薬理学 / トランスレーショナルリサーチ |
Outline of Final Research Achievements |
In the present study, we aimed to elucidate the mechanism of respiratory rhythm generation, focusing on the role of astrocytes in respiratory rhythm generation and hypoxic respiratory responsiveness. For this purpose, we used the isolated brainstem spinal cord preparation made of neonatal rats. We analyzed the neuronal and astrocytic activities in the medullary respiratory center by calcium imaging simultaneously recording neural respiratory output. We found that subsets of neurons and astrocytes showed oscillatory activities that were synchronized with inspiratory activities. The identified respiratory-synchronized activities of these astrocytes were not dependent on neuronal activities but spontaneous. Further, we found that TRPA1 channels expressed on the medullary astrocytes sense hypoxia and mediate augmenting hypoxic respiratory responsiveness.
|
Academic Significance and Societal Importance of the Research Achievements |
安静時のみでなく、運動時や睡眠中も、脳での呼吸調節により体内の酸素化状態を常に適正に保つことが重要であるが、脳はどのように呼吸リズムを形成し、酸素レベル低下時に呼吸を増強させるかは、解明されていない。本研究により、延髄呼吸中枢のグリア細胞・アストロサイトは、呼吸リズム形成において重要な役割を果たし、さらに低酸素のみでなく二酸化炭素によって興奮することが確かめられ、低酸素血症および高二酸化炭素血症を呈するCOPD等の呼吸器疾患症例における呼吸調節において重要な役割を果たしている可能性が示唆された。この成果は様々な呼吸調節障害症例の病態理解および新規治療法開発に基礎的知見を提供すると期待される。
|
Report
(5 results)
Research Products
(85 results)
-
-
-
-
-
-
-
[Journal Article] Substantial involvement of TRPM7 inhibition in the therapeutic effect of Ophiocordyceps sinensis on pulmonary hypertension.2021
Author(s)
Hiraishi K, Kurahara LH, Feng J, Yamamura A, Cui Y, Yahiro E, Yokomise H, Go T, Ishikawa K, Yokota N, Fujiwara A, Onitsuka M, Abe K, Ohga S, Satoh T, Okada Y, Yue L, Inoue R, Hirano K.
-
Journal Title
Translational Research
Volume: in press
Pages: 00054-2
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
[Journal Article] Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow.2020
Author(s)
Kono Y, Yokota S, Fukushi I, Arima Y, Onimaru H, Okazaki S, Takeda K, Yazawa I, Yoshizawa M, Hasebe Y, Koizumi K, Pokorski M, Toda T, Sugita K, Okada Y.
-
Journal Title
Sci Rep.
Volume: 10
Issue: 1
Pages: 13325-13325
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Functional and anatomical connectivity from the dorsomedial hypothalamus to the ventral medullary cardiovascular regions: possible neural substrate mediatingstress-induced sympathoexcitation.2018
Author(s)
Kono Y, Arima Y, Yokota S, Onimaru H, Fukushi I, Koizumi K, Hasebe Y, Yoshizawa M, Kise H, Hoshiai M, Sugita K, Toda T, Okada Y
Organizer
European Society of Cardiology Congress 2018
Related Report
Int'l Joint Research
-
[Presentation] Activation of astrocytes is requred for the persistence of poststress blood pressure elevation2018
Author(s)
Hasebe Y, Yokota S, Takeda K, Sugama S, Kono Y, Koizumi K, Fukushi I, Hoshiai M, Kakinuma Y, Pokorski M, Horiuchi J, Sugita K, Okada Y
Organizer
European Society of Cardiology Congress 2018
Related Report
Int'l Joint Research
-
-
[Presentation] Significance of medulla-spinal cord preparation of the newborn rat.2018
Author(s)
Fukushi I, Uchiyama M, Kurita Y, Yazawa I, Okazaki S, Hasebe Y, Kono Y, Yokota S, Takeda K, Mori Y, Onimaru H, Okada Y
Organizer
Society for Neuoscience Meeting (Neuoscience2018)
Related Report
Int'l Joint Research
-
[Presentation] Neural pathway supposedly mediating the descending autonomic information from the dorsomedial hypothalamus to the ventral medullary cardiorespiratory regions.2018
Author(s)
Okada Y, Kono Y, Arima Y, Yokota S, Onimaru H, Fukushi I, Koizumi K, Hasebe Y, Yoshizawa M, Kise H, Toda T
Organizer
Neuoscience Meeting (Neuoscience2018)
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
[Presentation] Anatomical connectivity from the dorsomedial hypothalamus to the ventral medullary cardiovascular regions: neural pathway mediating the descending sympathetic information2018
Author(s)
Kono Y, Arima Y, Yokota S, Onimaru H, Fukushi I, Koizumi K, Hasebe Y, Yoshizawa M, Kise H, Hoshiai M, Sugita K, Toda T, Okada Y
Organizer
第41回 日本神経科学大会
Related Report
-
-
-
-
-
[Presentation] Activated astrocytes induce persistence of post-stress blood pressure elevation2017
Author(s)
Hasebe Y, Sugama S, Takeda K, Koizumi K, Yokota S, Fukushi I, Hoshiai M, Kakinuma Y, Pokorski M, Horiuchi J, Sugita K, Okada Y
Organizer
International Society for Autonomic Neuroscience Meeting (ISAN 2017)
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-