Astrocytes perform a range of homeostatic and regulatory tasks that are critical for normal functioning of the central nervous system. In response to an injury or disease, astrocytes undergo a pronounced transformation into a reactive state that involves changes in the expression of many genes and dramatically changes astrocyte morphology and functions. This astrocyte reactivity is highly dependent on the initiating insult and pathological context. C3a is a peptide generated by the proteolytic cleavage of the third complement component. C3a has been shown to exert neuroprotective effects, stimulate neural plasticity and promote astrocyte survival but can also contribute to synapse loss, Alzheimer’s disease type neurodegeneration and blood–brain barrier dysfunction. To test the hypothesis that C3a elicits differential effects on astrocytes depending on their reactivity state, we measured the expression of Gfap, Nes, C3ar1, C3, Ngf, Tnf and Il1b in primary mouse cortical astrocytes after chemical ischemia, after exposure to lipopolysaccharide (LPS) as well as in control naïve astrocytes. We found that C3a down-regulated the expression of Gfap, C3 and Nes in astrocytes after ischemia. Further, C3a increased the expression of Tnf and Il1b in naive astrocytes and the expression of Nes in astrocytes exposed to LPS but did not affect the expression of C3ar1 or Ngf. Jointly, these results provide the first evidence that the complement peptide C3a modulates the responses of astrocytes in a highly context-dependent manner.

星形胶质细胞执行一系列稳态和调节任务，这些任务对中枢神经系统的正常功能至关重要。为应对损伤或疾病，星形胶质细胞会发生明显的转变，进入反应状态，这涉及许多基因表达的变化，并显着改变星形胶质细胞的形态和功能。这种星形胶质细胞反应性高度依赖于引发的侮辱和病理背景。C3a 是由第三补体成分的蛋白水解裂解产生的肽。C3a 已被证明具有神经保护作用，刺激神经可塑性并促进星形胶质细胞存活，但也可能导致突触丢失、阿尔茨海默病型神经变性和血脑屏障功能障碍。Gfap、Nes、C3ar1、C3、Ngf、Tnf和Il1b在化学缺血后、暴露于脂多糖 (LPS) 后以及对照幼稚星形胶质细胞中的原代小鼠皮质星形胶质细胞中。我们发现C3a下调缺血后星形胶质细胞中Gfap、C3和Nes的表达。此外，C3a 增加了幼稚星形胶质细胞中Tnf和Il1b的表达以及暴露于 LPS 的星形胶质细胞中Nes的表达，但不影响C3ar1或Ngf 的表达。共同地，这些结果提供了补体肽 C3a 以高度依赖环境的方式调节星形胶质细胞反应的第一个证据。