Protective roles of ATF6 and ATF4 in the mouse model of stroke
Project/Area Number |
24500419
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Nerve anatomy/Neuropathology
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Research Institution | Kanazawa University |
Principal Investigator |
KITAO Yasuko 金沢大学, 医学系, 協力研究員 (00019613)
|
Co-Investigator(Kenkyū-buntansha) |
HORI Osamu 金沢大学, 医学系, 教授 (60303947)
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Co-Investigator(Renkei-kenkyūsha) |
TAKARADA Mika 金沢大学, 医学系, 助教 (40565412)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 脳虚血 / 小胞体ストレス / アストロサイト / 脳梗塞 / 神経細胞死 / ATF6 / アストログリア / 脳梗塞モデル |
Outline of Final Research Achievements |
To dissect the role of the unfolded protein response (UPR) in brain ischemia, we investigated the relevance of ATF6α, a master transcriptional factor in the UPR, after middle cerebral artery occlusion (MCAO) in mice. Enhanced expression of GRP78, a downstream molecular chaperone of ATF6α, was observed in the peri-infarct region of wild-type mice after MCAO. Analysis using wild-type and Atf6α-/- mice revealed a larger infarct volume and increased cell death in the peri-ischemic region of Atf6α-/- mice 5 days after MCAO. These phenotypes in Atf6α-/- mice were associated with reduced levels of astroglial activation/glial scar formation, and a spread of tissue damage into the non-infarct area. Further analysis in mice and cultured astrocytes revealed that STAT3-GFAP signaling was diminished in Atf6α-/- astrocytes. These results suggest a critical role of the UPR for regulating astroglial activation and neuronal survival after brain ischemia.
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Deletion of Atf6α impairs astroglial activation and enhances neuronal death after brain ischemia in mice.2015
Author(s)
Yoshikawa A, KamideT, Hashida K, Ta HM, Inahata Y, Takarada-Iemata M, Hattori T, Mori K, Takahashi R, Matsuyama T, Hayashi Y, Kitao Y, Hori O
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Journal Title
J Neurochem.
Volume: 132(3)
Issue: 3
Pages: 342-53
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Anxiety- and depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson's disease.2014
Author(s)
Lopatina O, Yoshihara T, Nishimura T, Zhong J, Akther S, Fakhrul AA, Liang M, Higashida C, Sumi K, Furuhara K, Inahata Y, Huang JJ, Koizumi K, Yokoyama S, Tsuji T, Petugina Y, Sumarokov A, Salmina AB, Hashida K, Kitao Y, Hori O, Asano M, Kitamura Y, Kozaka T, Shiba K, Zhong F, Xie MJ, Sato M, Ishihara K, Higashida H.
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Journal Title
Front Behav Neurosci
Volume: 8
Pages: 1-18
DOI
Related Report
Peer Reviewed / Open Access
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