Developmental neuronal cell death has been characterized as a cell autonomous “suicide” program, but recent findings suggest that microglia play an active role in determining the survival of developing neurons. Results have been contradictory, however, with some studies concluding that microglia promote cell death, while others report that microglia are neuroprotective. Here, we depleted microglia throughout the newborn mouse brain using intracerebroventricular injections of clodronate liposomes, and examined effects on naturally occurring cell death across multiple brain areas. Microglial density varied significantly by brain region, and clodronate liposome treatment at birth reduced the number of microglia in all regions examined. The effect of microglia reduction on cell death, however, varied by region: the number of dying cells was reduced in the medial septum and medial amygdala in clodronate treated animals, but was increased in the oriens layer of the hippocampus, and unchanged in several other brain regions. In most brain regions, the average size of microglia was greater in microglia‐depleted than in control animals, suggesting that the remaining microglia compensate to some extent for a reduction in microglial number. The hippocampal oriens was exceptional in this regard, in that microglial size was reduced following treatment with clodronate. Microglia produce cytokines which mediate many of their effects, and we found higher expression of inflammatory cytokines in the hippocampus than in the septum, independent of clodronate treatment. Thus, microglial depletion has opposite effects on cell death in different brain regions of the newborn brain, which may be related to regional heterogeneity in microglia.

中文翻译：

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小胶质细胞耗竭导致小鼠大脑中发育神经元细胞死亡的区域特定变化。

发育性神经元细胞死亡已被描述为一种细胞自主的“自杀”程序，但最近的发现表明小胶质细胞在决定发育中的神经元的存活中起着积极的作用。然而，结果却相矛盾，有些研究认为小胶质细胞会促进细胞死亡，而另一些研究则表明小胶质细胞具有神经保护作用。在这里，我们使用脑室注射氯膦酸盐脂质体消灭了整个新生小鼠大脑的小胶质细胞，并研究了对多个大脑区域自然发生的细胞死亡的影响。小胶质细胞密度随大脑区域的变化而显着变化，出生时使用氯膦酸盐脂质体治疗可减少所有检查区域的小胶质细胞数量。小胶质细胞减少对细胞死亡的影响因地区而异：在用氯膦酸盐处理过的动物中，中隔和中杏仁核的垂死细胞数量减少了，但是海马的oriens层中的死亡细胞数量增加了，而其他几个大脑区域则没有变化。在大多数大脑区域，贫化的小胶质细胞比对照动物的小胶质细胞的平均大小更大，这表明剩余的小胶质细胞在一定程度上补偿了小胶质细胞数量的减少。在这方面，海马oriens是例外的，因为氯膦酸盐治疗后小胶质细胞的大小减小了。小胶质细胞产生介导其许多作用的细胞因子，我们发现海马中炎症细胞因子的表达高于隔膜，与氯膦酸盐治疗无关。从而，