Protective roles of ATF6 and ATF4 in the mouse model of stroke

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500419
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• 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)
• Co-Investigator(Renkei-kenkyūsha): TAKARADA Mika 金沢大学, 医学系, 助教 (40565412)
• Project Period (FY): 2012-04-01 – 2015-03-31
• 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.

Free Research Field

神経解剖学