Evaluation of phagocytic function and analysis of antigen-processing mechanism of microglia in ALS

首先，我们用免疫组织化学方法观察ALS小鼠脊髓损伤后小胶质细胞的行为。我们发现症状期SOD1G85R转基因小鼠脊髓中的小胶质细胞摄取或包围SOD1聚集体。因此，我们认为这些小胶质细胞反映了当小胶质细胞不能完全消化SOD 1聚集体时的“吞噬功能受挫“状态。然后，为了定量小胶质细胞对聚集体的摄取，我们建立了吞噬细胞荧光珠掺入量的测定系统，利用该系统，我们将表达SOD 1G85 R的小胶质细胞与野生型小胶质细胞进行了比较，但没有发现差异，我们证实了SOD 1WT或G85 R纤维的聚集体在加入到培养基中时被掺入到小胶质细胞中。然后，我们通过将SOD1G85R吸附到珠粒中来制备突变的SOD1聚集体模拟物，并检测野生型或表达SOD1G85R的小胶质细胞整合它们的能力，但没有发现差异。

First, we evaluatebyimmunohistochemistry the microglialbehaviorinspinalcord lesion of ALS mouse model. We found microglia uptaked, or surrounded the SOD1 aggregates in the spinal cord of the SOD1G85R transgenic mouse at symptomatic stage. Therefore wehy pothes ized that these microglia reflected the state of"frustrated phagocytosis"when microglia could not digest SOD1 aggregates fully. Next, in order to quantify th uptake of aggregates into microglia, we establishedthe system tomeasure the fluorescent beads incorporated into the phagocytes Using the system, we compared the SOD1G85R expressing-microglia with wild-type ones, but no difference was found. We confirmedtheaggregates ofthe SOD1WTor G85Rfibrilswere incorpotrated into microglia when they were added into medium. Then we made the mutant SOD1 aggregate-mimics by adsorb SOD1G85Rinto beads andexamined the ability ofwild-type orSOD1G85R-expressing microglia t incorporate them, butno difference was found.