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

• Published in: Cellular and molecular neurobiology Vol. 44; no. 1; p. 48
• Main Authors: Muhamad, Nor Atiqah, Masutani, Kohei, Furukawa, Shota, Yuri, Shunsuke, Toriyama, Michinori, Matsumoto, Chuya, Itoh, Seiya, Shinagawa, Yuichiro, Isotani, Ayako, Toriyama, Manami, Itoh, Hiroshi
• Format: Journal Article
• Language: English
• Published: New York Springer US 2024; Springer Nature B.V
• Subjects: Animal models; Animals; Apoptosis; Apoptosis - drug effects; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Biomedical and Life Sciences; Biomedicine; Brief Report; Calcium signalling; Cell Biology; Cilia - drug effects; Cilia - metabolism; Complement C3 - metabolism; Inflammation; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurobiology; Neurodegenerative diseases; Neurosciences; Neurotoxicity; Pattern recognition; Potentiation; Primary cilium; Astrocytes; Conditional knockout mouse; TRPV4; LPS
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-024-01482-5

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 Ca 2+ 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. Graphical Abstract The primary cilium of astrocytes are required for the C3 expression in reactive astrocytes. Furthermore, the potentiation of calcium signalling appears to be involved in the promotion of C3 expression in reactive astrocytes.