Microglial activation in brain lesions with tau deposits:: Comparison of human tauopathies and tau transgenic mice TgTauP301L

被引：64

作者：

Sasaki, Atsushi ^{[1
]}

Kawarabayashi, Takeshi ^{[2
]}

Murakami, Tetsuro ^{[3
]}

Matsubara, Etsuro ^{[4
]}

Ikeda, Masaki ^{[5
]}

Hagiwara, Haruo ^{[6
]}

Westaway, David ^{[7
]}

George-Hyslop, Peter S. ^{[7
]}

Shoji, Mikio ^{[2
]}

Nakazato, Yoichi ^{[1
]}

机构：

[1] Gunma Univ, Grad Sch Med, Dept Human Pathol, Gunma 3718511, Japan

[2] Hirosaki Univ, Grad Sch Med, Dept Neurol, Aomori, Japan

[3] Okayama Univ, Grad Sch Med, Dept Neurol Neurosci Biophysiol Sci, Okayama, Japan

[4] Natl Ctr Geriatr & Gerontol, Natl Inst Longev Sci, Dept Alzheimers Dis Res, Aichi, Japan

[5] Gunma Univ, Grad Sch Med, Dept Neurol, Gunma 3718511, Japan

[6] Gunma Univ, Grad Sch Med, Dept Anat & Cell Biol, Gunma 3718511, Japan

[7] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

来源：

BRAIN RESEARCH | 2008年 / 1214卷

基金：

英国惠康基金;

关键词：

microglia; tau; transgenic mice; Iba1; AT8; MHC class II;

D O I：

10.1016/j.brainres.2008.02.084

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

The aim of this study is to clarify the relationship of microglia to phosphorylated tau accumulation and the characteristics of microglial activation in brain lesions of human tauopathies in comparison to mutant tau transgenic (TG) mice. We performed immunocytochemical analyses of brains from six patients with tauopathies, and 24 mice (18 TG mice expressing mutant tau P301L and six non-TG control mice, 11 to 27 months of age) using anti-tau antibodies and various microglial markers. In the tau TG, both semiquantitative severity ratings of microglial activation and an ultrastructural study were performed. In human tauopathies, Iba1- and major histocompatibility complex (MHC) class II-positive activated microglia increased in regions of phosphorylated tau (AT8) accumulation. The immunoreactivity of scavenger receptor class A (SRA) was present in some activated microglia, including phagocytic microglia in Alzheimer's disease (AD). Double-immunofluorescent analysis under a confocal microscope showed activated microglia at the vicinity of AT8-positive cells. Semiquantitative data of the TG and control mice indicated that the immunopositivity of AT8 was closely associated with the number of Iba1-positive microglia in the cortical area. Tau-associated microglia showed rare immunoreactivity for MHC class II antigen and SRA in the TG mice. Ultrastructurally, activated microglia with enlarged cytoplasm were located near neurons containing abnormal cytoskeletons. This comparative study of human tauopathies and tau TG mice indicated that microglial activation was closely related to phosphorylated tau accumulation, and that activated microglia of the TG mice may have the low expression of MHC class II and SRA compared with those of human tauopathies. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：159 / 168

页数：10

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