Astrocyte-Specific Inhibition of the Primary Cilium Suppresses C3 Expression in Reactive Astrocyte.

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2024-06-01 DOI:10.1007/s10571-024-01482-5
Nor Atiqah Muhamad, Kohei Masutani, Shota Furukawa, Shunsuke Yuri, Michinori Toriyama, Chuya Matsumoto, Seiya Itoh, Yuichiro Shinagawa, Ayako Isotani, Manami Toriyama, Hiroshi Itoh
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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.

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星形胶质细胞特异性抑制初级纤毛可抑制反应性星形胶质细胞的 C3 表达
C3 阳性反应性星形胶质细胞在各种神经退行性疾病中发挥着神经毒性作用。然而,控制 C3 阳性反应性星形胶质细胞诱导的机制在很大程度上是未知的。我们发现,C3 阳性反应性星形胶质细胞中接收细胞外信号的细胞器--初级纤毛的长度增加,而初级纤毛的缺失或缩短会减少 C3 阳性反应性星形胶质细胞的数量。药理实验表明,Ca2+ 信号可能会协同促进反应性星形胶质细胞中 C3 的表达。条件性基因敲除(cKO)小鼠在药物刺激下可特异性抑制星形胶质细胞中初级纤毛的形成,即使在注射脂多糖(LPS)后,其脑中 C3 阳性反应性星形胶质细胞和凋亡细胞的比例也会下降。此外,在 cKO 小鼠身上观察到的新物体识别(NOR)得分高于在神经炎症模型小鼠身上观察到的得分。这些结果表明,星形胶质细胞中的初级纤毛对 C3 的表达具有正向调节作用。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一种新策略。
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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