Molecular pathologic study on pathogenesis of HIV-associated neurocognitive disorders (HANDs)

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461285
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kagoshima University
• Principal Investigator: IZUMO Syuji 鹿児島大学, 医歯学域医学系, 教授 (30143811)
• Co-Investigator(Kenkyū-buntansha): KUBOTA RYUJI 鹿児島大学, 医歯学域医学系, 准教授 (70336337) ; FURUKAWA YOSHITAKA 医歯学域医学部, 歯学部附属病院, 講師 (00359978)
• Co-Investigator(Renkei-kenkyūsha): MORI KAZYYASU 国立感染症研究所, 研究員 (20270655)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 神経病理学 / ウイルス / 認知障害 / 神経免疫学

Outline of Final Research Achievements

To understand the pathogenesis of HIV-1 associated neurocognitive disorders (HANDs) we immunohistochemically analyzed brains from simian immunodeficiency virus (SIV)-macaque models and autopsy brains from HIV-1-infected individuals. A highly virulent SIV302-2-infected animals efficiently developed SIV encephalitis with multinuclear giant cells. Concerning the cortical degenerative changes, astrocyte-specific functional molecules, EAAT-2, AQP4, and connexin43 were proportionally reduced in the frontal cortex, and neuronal, as well as astrocytic, apoptosis was observed. A double immunohistochemistry demonstrated that reduction of AQP4 preceded EAAT-2 reduction, suggesting that a primary damage of astrocyte and blood-brain barrier disturbance induce excitatory neuronal cell death. Menin and TGF-beta were expressed in the apoptotic neurons suggesting their roles in pathogenesis of HANDs. These data confirm two independent pathogenic processes in HANDs.

Free Research Field

医歯薬学　神経内科学