Morphological and Phagocytic Profile of Microglia in the Developing Rat Cerebellum.
Morphological and Phagocytic Profile of Microglia in the Developing Rat Cerebellum.
复制标题
发育中的大鼠小脑中小胶质细胞的形态和吞噬性。
DOI：
10.1523/eneuro.0036-15.2015
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发表时间：
2015-07
期刊：
影响因子：
3.4
通讯作者：
McCarthy MM
中科院分区：
文献类型：
--
作者：
Perez-Pouchoulen M;VanRyzin JW;McCarthy MM
人们越来越认识到小胶质细胞在神经发育中起着重要作用。小脑在出生后成熟，经历主要生长，但小胶质细胞在小脑发育中的作用尚不清楚。使用实验室大鼠，我们使用基于设计的无偏体视学方法对整个蚓部和整个发育过程中的小胶质细胞进行了量化和形态学分类。我们发现，在出生后的前3周，小胶质细胞形态以特定区域的方式从变形虫转变为分枝。这些形态变化伴随着在P17至P19出生后第三周突然出现的吞噬杯，与第一周相比增加了约四倍，随后在第三周结束时迅速下降。在3 d窗口内，颗粒层（~ 69%）的小胶质细胞吞噬杯明显高于分子层（ML; ~ 31%），并且存在于~ 67%的粗突小胶质细胞和~ 33%的细突小胶质细胞中。在ML中发现了类似比例的与小胶质细胞相关的吞噬杯，无论是厚的还是薄的。我们在一些小胶质吞噬杯中观察到细胞核断裂和裂解的caspase-3表达，可能来自垂死的颗粒神经元。在P17时，男性的薄突小胶质细胞比女性增加了大约两倍。我们的研究结果表明，小胶质细胞成熟的连续过程和小胶质细胞在小脑皮层的不均匀分布暗示小胶质细胞是发育中的小脑的重要细胞组成部分。
Microglia are being increasingly recognized as playing important roles in neurodevelopment. The cerebellum matures postnatally, undergoing major growth, but the role of microglia in the developing cerebellum is not well understood. Using the laboratory rat we quantified and morphologically categorized microglia throughout the vermis and across development using a design-based unbiased stereology method. We found that microglial morphology changed from amoeboid to ramified during the first 3 postnatal weeks in a region specific manner. These morphological changes were accompanied by the sudden appearance of phagocytic cups during the third postnatal week from P17 to P19, with an approximately fourfold increase compared with the first week, followed by a prompt decline at the end of the third week. The microglial phagocytic cups were significantly higher in the granular layer (∼69%) than in the molecular layer (ML; ∼31%) during a 3 d window, and present on ∼67% of microglia with thick processes and ∼33% of microglia with thin processes. Similar proportions of phagocytic cups associated to microglia with either thick or thin processes were found in the ML. We observed cell nuclei fragmentation and cleaved caspase-3 expression within some microglial phagocytic cups, presumably from dying granule neurons. At P17 males showed an approximately twofold increase in microglia with thin processes compared with females. Our findings indicate a continuous process of microglial maturation and a nonuniform distribution of microglia in the cerebellar cortex that implicates microglia as an important cellular component of the developing cerebellum.