Comparative morphometric analysis of microglia in the spinal cord of SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis.
Comparative morphometric analysis of microglia in the spinal cord of SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis.
复制标题
肌萎缩侧索硬化症 SOD1G93A 转基因小鼠模型脊髓小胶质细胞的比较形态测量分析。
DOI：
10.1111/ejn.13227
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发表时间：
2016
期刊：
影响因子：
3.4
通讯作者：
Jinno S.
中科院分区：
文献类型：
--
作者：
Ohgomori T;Yamada J;Takeuchi H;Kadomatsu K;Jinno S.
反应性小胶质细胞伴随着形态学改变而发生一系列表型变化。然而，小胶质细胞的形态学分类尚未实现。为了解决这个问题，我们在此对肌萎缩侧索硬化症模型SOD 1G 93 A转基因小鼠腰髓腹角中的离子钙结合适配分子1免疫反应性（Iba 1+）小胶质细胞进行了三维重建形态学分析。分层聚类分析显示，小胶质细胞可分为4类：S型（以监视型小胶质细胞命名）和R1、R2、R3型（以反应型小胶质细胞命名）。为了比较形态测量学，我们还使用野生型小鼠分析了两种药理学疾病模型：3，3 ′-亚氨基二丙腈（IDPN）诱导的轴突病和脂多糖（LPS）诱导的神经炎症。S型小胶质细胞显示出监视性小胶质细胞的典型分枝形态，并且大多数在野生型对照中观察到。R1型小胶质细胞在SOD 1G 93 Amice中的疾病早期观察到，并且也经常发生在IDPN治疗的小鼠中。细胞体小，突起短而简单。R2型小胶质细胞在形态上与R1型小胶质细胞相似，但仅在SOD 1G 93 Amice和IDPN治疗小鼠的疾病中期短暂出现。R3型小胶质细胞表现出浓密的形状，并在SOD 1G 93 Amice和LPS处理的小鼠中的疾病末期观察到。这些结果表明，SOD 1G 93 Amice的小胶质细胞可以分为四种类型，也表明表型变化可能是由轴突病变和神经炎症相关事件引起的。
It has long been recognized that reactive microglia undergo a series of phenotypic changes accompanying morphological transformation. However, the morphological classification of microglia has not yet been achieved. To address this issue, here we morphometrically analysed three‐dimensionally reconstructed ionized calcium binding adaptor molecule 1‐immunoreactive (Iba1+) microglia in the ventral horn of the lumbar spinal cord of SOD1G93Atransgenic mice, a model of amyotrophic lateral sclerosis. The hierarchical cluster analysis revealed that microglia were objectively divided into four groups: type S (named after surveillant microglia) and types R1, R2 and R3 (named after reactive microglia). For the purpose of comparative morphometry, we also analysed two pharmacological disease models using wild‐type mice: 3,3′‐iminodipropionitrile (IDPN)‐induced axonopathy and lipopolysaccharide (LPS)‐induced neuroinflammation. Type S microglia showed a typical ramified morphology of surveillant microglia, and were mostly observed in wild‐type controls. Type R1 microglia were seen at the early stage of disease in SOD1G93Amice, and also frequently occurred in IDPN‐treated mice. They exhibited small cell bodies with shorter and simple processes. Type R2 microglia were morphologically similar to type R1 microglia, but only transiently occurred in the middle stage of disease in SOD1G93Amice and in IDPN‐treated mice. Type R3 microglia exhibited a bushy shape, and were observed in the end stage of disease in SOD1G93Amice and in LPS‐treated mice. These findings indicate that microglia of SOD1G93Amice can be classified into four types, and also suggest that the phenotypic changes may be induced by the events related to axonopathy and neuroinflammation.