PDF(Pubmed)
Abstract：
C3-positive reactive astrocytes play a neurotoxic role in various neurodegenerative diseases. However, the mechanisms controlling C3-positive reactive astrocyte induction are largely unknown. We found that the length of the primary cilium, a cellular organelle that receives extracellular signals was increased in C3-positive reactive astrocytes, and the loss or shortening of primary cilium decreased the count of C3-positive reactive astrocytes. Pharmacological experiments suggested that Ca2+ signalling may synergistically promote C3 expression in reactive astrocytes. Conditional knockout (cKO) mice that specifically inhibit primary cilium formation in astrocytes upon drug stimulation exhibited a reduction in the proportions of C3-positive reactive astrocytes and apoptotic cells in the brain even after the injection of lipopolysaccharide (LPS). Additionally, the novel object recognition (NOR) score observed in the cKO mice was higher than that observed in the neuroinflammation model mice. These results suggest that the primary cilium in astrocytes positively regulates C3 expression. We propose that regulating astrocyte-specific primary cilium signalling may be a novel strategy for the suppression of neuroinflammation.
摘要：
C3阳性反应性星形胶质细胞在各种神经退行性疾病中起神经毒性作用。然而,控制C3阳性反应性星形胶质细胞诱导的机制尚不清楚.我们发现初级纤毛的长度，接受细胞外信号的细胞器在C3阳性反应性星形胶质细胞中增加，初级纤毛的丢失或缩短会降低C3阳性反应性星形胶质细胞的数量。药理学实验表明，Ca2信号传导可以协同促进反应性星形胶质细胞中C3的表达。即使在注射脂多糖（LPS）后，在药物刺激下特异性抑制星形胶质细胞中原代纤毛形成的条件性敲除（cKO）小鼠的脑中C3阳性反应性星形胶质细胞和凋亡细胞的比例也降低。此外,在cKO小鼠中观察到的新物体识别（NOR）评分高于神经炎症模型小鼠。这些结果表明，星形胶质细胞中的原代纤毛正调节C3表达。我们认为，调节星形胶质细胞特异性初级纤毛信号可能是抑制神经炎症的新策略。
