2014 Fiscal Year Final Research Report
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)
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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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Keywords | 脳虚血 |
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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Free Research Field |
神経解剖学
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