RRC ID 88555
著者 Muhamad NA, Masutani K, Furukawa S, Yuri S, Toriyama M, Matsumoto C, Itoh S, Shinagawa Y, Isotani A, Toriyama M, Itoh H.
タイトル Astrocyte-Specific Inhibition of the Primary Cilium Suppresses C3 Expression in Reactive Astrocyte.
ジャーナル Cell Mol Neurobiol
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.
巻・号 44(1)
ページ 48
公開日 2024-6-1
DOI 10.1007/s10571-024-01482-5
PII 10.1007/s10571-024-01482-5
PMID 38822888
PMC PMC11144130
MeSH Animals Apoptosis / drug effects Astrocytes* / drug effects Astrocytes* / metabolism Cilia* / drug effects Cilia* / metabolism Complement C3 / metabolism Lipopolysaccharides / pharmacology Mice Mice, Inbred C57BL Mice, Knockout*
リソース情報
実験動物マウス RBRC02350