Associated occurrence of p75 neurotrophin receptor expressing aldynoglia and microglia/macrophages in long term organotypic murine brain slice cultures
Associated occurrence of p75 neurotrophin receptor expressing aldynoglia and microglia/macrophages in long term organotypic murine brain slice cultures
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长期器官型小鼠脑切片培养中表达 p75 神经营养蛋白受体的脑胶质细胞和小胶质细胞/巨噬细胞的相关发生
DOI：
10.1016/j.brainres.2014.11.027
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发表时间：
2015
期刊：
影响因子：
2.9
通讯作者：
W Baumgärtner
中科院分区：
文献类型：
--
作者：
Spitzbarth I;Cana A;Hahn K;Hansmann F;W Baumgärtner
以表达原型未成熟许旺细胞标志物p75神经营养因子受体（NTR）为特征的促进生长的痛觉神经胶质细胞已被证明在一些脱髓鞘疾病中发生。然而，决定这些细胞的出现和命运的机制在很大程度上是未知的。本研究旨在通过体外切片培养的方法来鉴定这些细胞和潜在的触发因素。成年小鼠器官型大脑和脑干切片体外培养18天。免疫组化检测p75 NTR、CD 107 b、周蛋白、生长相关蛋白（GAP）-43和胶质细胞酸性蛋白（GFAP）。用原位杂交证实了p75 NTR的结果。培养与双至多极p75 NTR阳性，但周蛋白阴性的神经胶质细胞的自发发生的逐渐增加有关，这表明阿氏神经胶质细胞施万细胞样细胞。类似的细胞对GAP-43染色呈强阳性，GAP-43是非髓鞘形成的雪旺细胞的标志物。p75 NTR阳性胶质细胞的数量与GFAP表达无关，但与CD 107 b阳性吞噬小胶质细胞/巨噬细胞的显著自发反应有很强的相关性。此外，aldynoglial p75 NTR免疫反应性呈负相关的神经元p75 NTR的表达，这是在培养过程中丢失。本研究结果表明，培养器官型小鼠脑切片伴随着小胶质细胞/巨噬细胞和p75 NTR阳性细胞的自发反应，提示雪旺细胞样aldynoglia。研究结果强调了小胶质细胞/巨噬细胞的作用，这似乎是一个重要的触发因素，促进了这种独特类型的大胶质细胞的发生。
Growth-promoting aldynoglia, characterized by the expression of the prototype immature Schwann cell marker p75 neurotrophin receptor (NTR) have been shown to occur in some demyelinating diseases. However, the mechanisms determining the emergence and fate of such cells are largely unknown. This study aimed at the identification of such cells and potential triggering factors using anin vitroslice culture approach. Organotypic cerebrum and brain stem slices of adult mice were cultivated for up to 18 daysin vitro. Immunohistochemistry for the detection of p75NTR, CD107b, periaxin, growth associated protein (GAP)-43, and glial fibrillary acidic protein (GFAP) was performed. The results for p75NTRwere substantiated by the use ofin situhybridization. Cultivation was associated with a progressively increasing spontaneous occurrence of bi- to multipolar p75NTR-positive, but periaxin-negative glia, indicative of aldynoglial Schwann cell like cells. Similar cells stained intensely positive for GAP-43, a marker for non-myelinating Schwann cells. The number of p75NTRpositive glia did not correlate with GFAP expression, but showed a strong correlation with a remarkable spontaneous response of CD107b positive phagocytic microglia/macrophages. Moreover, aldynoglial p75NTRimmunoreactivity negatively correlated to neuronal p75NTRexpression, which was lost during culturing. The present results demonstrate that the cultivation of organotypic murine brain slices is accompanied by a spontaneous response of both microglia/macrophages and p75NTRpositive cells, suggestive of Schwann cell like aldynoglia. The findings highlights the role of microglia/macrophages, which seem to be an important triggering factor, facilitating the occurrence of this unique type of macroglia.
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