Appearance of Phagocytic Microglia Adjacent to Motoneurons in Spinal Cord Tissue From a Presymptomatic Transgenic Rat Model of Amyotrophic Lateral Sclerosis
Appearance of Phagocytic Microglia Adjacent to Motoneurons in Spinal Cord Tissue From a Presymptomatic Transgenic Rat Model of Amyotrophic Lateral Sclerosis
复制标题
DOI：
10.1002/jnr.22424
复制
发表时间：
2010-09-01
影响因子：
4.2
通讯作者：
Ohsawa, Keiko
中科院分区：
文献类型：
--
作者：
Sanagi, Tomomi;Yuasa, Shigeki;Ohsawa, Keiko
小胶质细胞活化发生在肌萎缩侧索硬化症(ALS)发病的早期。最近的证据表明，突变的Cu2+/Zn2+超氧化物歧化酶1(SOD1)在小胶质细胞中的表达与ALS的晚期疾病进展有关。然而，小胶质细胞影响ALS神经退行性变过程和疾病进展的机制尚不清楚。在本研究中，我们揭示了家族性ALS动物模型--症状前突变型SOD1(H46R)转基因大鼠的腰髓内可见活化的小胶质细胞聚集。聚集的小胶质细胞表达增殖细胞标记物Ki67、吞噬标记蛋白ED1和主要组织相容性复合体(MHC)II类。靠近小胶质细胞集合体的运动神经元呈弱的胆碱乙酰转移酶(ChAT)免疫反应，镜下可见颗粒内质网减少和核电子结构改变。此外，肿瘤坏死因子-α(TNF-α)和单核细胞趋化蛋白-1(MCP-1)免疫阳性信号定位于聚集的小胶质细胞。这些结果表明，激活和聚集的小胶质细胞表现出吞噬功能，以响应运动神经元的早期变化，并可能在症状前阶段ALS疾病的进展中发挥重要作用。(C)2010年Wiley-Liss公司
Microglial activation occurs early during the pathogenesis of amyotrophic lateral sclerosis (ALS). Recent evidence indicates that the expression of mutant Cu2+/Zn2+ superoxide dismutase 1 (SOD1) in microglia contributes to the late disease progression of ALS. However, the mechanism by which microglia influence the neurodegenerative process and disease progression in ALS remains unclear. In this study, we revealed that activated microglia aggregated in the lumbar spinal cord of presymptomatic mutant SOD1(H46R) transgenic rats, an animal model of familial ALS. The aggregated microglia expressed a marker of proliferating cell, Ki67, and phagocytic marker proteins ED1 and major histocompatibility complex (MHC) class II. The motoneurons near the microglial aggregates showed weak choline acetyltransferase (ChAT) immunoreactivity and contained reduced granular endoplasmic reticulum and altered nucleus electron microscopically. Furthermore, immunopositive signals for tumor necrosis factor-alpha (TNF alpha) and monocyte chemoattractant protein-1 (MCP-1) were localized in the aggregated microglia. These results suggest that the activated and aggregated microglia represent phagocytic features in response to early changes in motoneurons and possibly play an important role in ALS disease progression during the presymptomatic stage. (C) 2010 Wiley-Liss, Inc.