Loss of PRMT1 in the central nervous system (CNS) induces reactive astrocytes and microglia during postnatal brain development. Issue 6 (12th September 2020)

• Record Type: Journal Article
• Authors: Hashimoto, Misuzu; Kumabe, Ayako; Kim, Jun‐Dal; Murata, Kazuya; Sekizar, Sowmya; Williams, Anna; Lu, Weizhe; Ishida, Junji; Nakagawa, Tsutomu; Endo, Mitsuharu; Minami, Yasuhiro; Fukamizu, Akiyoshi
• Is Part Of: Journal of neurochemistry. Volume 156:Issue 6(2021)
• Page Start: 834
• Page End: 847
• Publication Date: 2020-09-12
• Subjects: astrocyte -- central nervous system (CNS) -- inflammation -- microglia -- PRMT1 -- transcriptome; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.15149
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: PRMT1, a major arginine methyltransferase, plays critical roles in transcription, DNA damage response, and cell proliferation. Although we have previously discovered the crucial roles of PRMT1 for oligodendrocyte lineage progression in the central nervous system of neural stem cell‐specific PRMT1 conditional knockout (PRMT1‐CKO) mice, the context of other glial cell states that may cause the hypomyelination phenotype in PRMT1‐CKO mice has not been explored so far. Here, we performed RNA‐seq of the neonatal cortices of PRMT1‐CKO mice to reveal overall gene expression changes and show the up‐regulation of inflammatory signaling which is generally mediated by astrocytes and microglia in advance of the myelination defects. In particular, qRT‐PCR analyses revealed Interleukin‐6 ( Il‐6 ), a major central nervous system cytokine, was dramatically increased in the PRMT1‐CKO brains. The gene expression changes led to augmentation of glial fibrillary acidic protein and Vimentin protein levels in PRMT1‐CKO mice, showing severe reactive astrogliosis after birth. We further show that IBA1‐positive and CD68‐positive activated microglia were increased in PRMT1‐CKO mice, in spite of intact Prmt1 gene expression in purified microglia from the mutant mice. Our results indicate that PRMT1 loss in the neural stem cell lineage causes disruptive changes in all glial types perturbing postnatal brain development and myelination. Abstract : We have previously shown that loss of protein arginine methyltransferase 1 (PRMT1) in the neural stem cells causes severe hypomyelination during development. Here, we report up‐regulation of inflammatory genes (e.g., Interleukin‐6 ( Il‐6 )) along with microgliosis and astrogliosis in the PRMT1‐deficient brain before the onset of hypomyelination. Our study suggests essential roles of PRMT1 not only in the oligodendrocyte lineage but also in all the glial lineages for proper brain development.