Department of Neuroscience, section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Allen Institute for Brain Science, Seattle, USA.
Acta Neuropathol Commun. 2015 May 23;3:31. doi: 10.1186/s40478-015-0203-5.
Microglia are tissue macrophages of the central nervous system that monitor brain homeostasis and react upon neuronal damage and stress. Aging and neurodegeneration induce a hypersensitive, pro-inflammatory phenotype, referred to as primed microglia. To determine the gene expression signature of priming, the transcriptomes of microglia in aging, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS) mouse models were compared using Weighted Gene Co-expression Network Analysis (WGCNA).
A highly consistent consensus transcriptional profile of up-regulated genes was identified, which prominently differed from the acute inflammatory gene network induced by lipopolysaccharide (LPS). Where the acute inflammatory network was significantly enriched for NF-κB signaling, the primed microglia profile contained key features related to phagosome, lysosome, antigen presentation, and AD signaling. In addition, specific signatures for aging, AD, and ALS were identified.
Microglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects.
小胶质细胞是中枢神经系统的组织巨噬细胞，可监测大脑的动态平衡，并在神经元损伤和应激时做出反应。衰老和神经退行性变会诱导一种超敏、促炎表型，称为激活的小胶质细胞。为了确定激活的基因表达特征，使用加权基因共表达网络分析（WGCNA）比较了衰老、阿尔茨海默病（AD）和肌萎缩侧索硬化症（ALS）小鼠模型中小胶质细胞的转录组。
鉴定出一个高度一致的上调基因的共识转录谱，该谱与脂多糖（LPS）诱导的急性炎症基因网络明显不同。急性炎症网络显著富集 NF-κB 信号，而激活的小胶质细胞谱包含与吞噬体、溶酶体、抗原呈递和 AD 信号相关的关键特征。此外，还鉴定出了与衰老、AD 和 ALS 相关的特定特征。
小胶质细胞激活诱导了一个高度保守的转录特征，具有衰老和疾病特异性方面。
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