The examination of AD pathology from the perspective of the astrocyte-neuron interaction: the participation of IGFBP-3 released by astrocytes.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461270
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyoto University
• Principal Investigator: Uemura Kengo 京都大学, 医学研究科, 非常勤講師 (00378663)
• Co-Investigator(Renkei-kenkyūsha): KINOSHITA Ayae 京都大学, 医学研究科, 教授 (80321610)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経分子病態学 / 認知症 / 脳、神経

Outline of Final Research Achievements

We presumed that astrocytes might trigger neuronal reactions, leading to tau phosphorylation. In this study, we examined AD pathology from the perspective of the astrocyte-neuron interaction. A cytokine-array analysis revealed that Abeta stimulates astrocytes to release several chemical mediators that are primarily related to inflammation and cell adhesion. Among those mediators, insulin-like growth factor (IGF)-binding protein 3 (IGFBP-3) was highly upregulated. In this study, we found that IGF-Ι suppressed tau phosphorylation induced by Abeta, although IGFBP-3 inhibited this property of IGF-Ι. As a result, IGFBP-3 contributed to tau phosphorylation and cell death induced by Abeeta. Our study suggested that calcineurin in astrocytes was activated by Abeta, leading to IGFBP-3 release. We further demonstrated that IGFBP-3 produced by astrocytes induced tau phosphorylation in neurons. Our study provides novel insights into the role of astrocytes in the induction of tau phosphorylation.

Free Research Field

医歯薬学