Circ_19038 and lnc-AK016022 synergistically regulate Sirt1 to promote remyelination and alleviate white matter injury in preterm mice

• Published in: Archives of biochemistry and biophysics 2024-10, Vol.760, p.110108, Article 110108
• Main Authors: Wei, Simeng, Xiao, Mi, Hu, Yuxin, Chang, Yuzhu, Wang, Fanghui, Liu, Li
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Brain - pathology; Circ_19038; Female; Inflammation; Lipopolysaccharides - toxicity; lnc-AK016022; Mice; Mice, Inbred C57BL; Pregnancy; Premature Birth; Preterm brain injury; Remyelination; RNA, Circular - genetics; RNA, Circular - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sirt1; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; White Matter - injuries; White Matter - metabolism; White Matter - pathology
• ISSN: 0003-9861; 1096-0384; 1096-0384
• DOI: 10.1016/j.abb.2024.110108

Maternal inflammation can lead to premature birth and fetal brain damage. CircRNA_19038 and lncRNA-AK016022 have been shown to be significantly reduced in brain tissues of preterm mice, while whether they are involved in the regulation of preterm white matter injury remains to be explored. Pregnant mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish a preterm brain injury model. Healthy mice born at term served as controls. Lentivirus-mediated circ_19038 overexpression vector (LV-circ_19038), LV-lnc-AK016022, LV-Sirt1 and LV-sh-Sirt1 were administered to preterm mice through the ventricles. The expression levels of circ_19038, lnc-AK016022 and Sirt1 in the brain tissues of preterm mice were significantly lower than those of full-term healthy mice, and circ_19038 and lnc-AK016022 were co-localized in the brain tissues. Upregulation of circ_19038 or/and lnc-AK016022 promoted remyelination and alleviated white matter structural damage, neuroinflammation, and long-term cognitive and motor deficits in preterm mice, and the combined effect of circ_19038 and lnc-AK016022 showed better results. Primary mouse neuronal cells were isolated to investigate the regulatory effects of circ_19038 and lnc-AK016022 on Sirt1. Circ_19038 and lnc-AK016022 jointly promoted the expression of Sirt1 by adsorbing miR-1b and miR-328, respectively. Moreover, silencing Sirt1 antagonized the beneficial effects of circ_19038 or/and lnc-AK016022 on brain white matter injury in preterm mice. In conclusion, circ_19038 and lnc-AK016022 synergistically regulated Sirt1 expression to promote remyelination and alleviate white matter injury in preterm mice. [Display omitted] •Circ_19038 and lnc-AK016022 were reduced and co-localized in preterm mouse brain.•Upregulation of circ_19038/lnc-AK016022 promoted remyelination in preterm mice.•Increase of circ_19038/lnc-AK016022 alleviated white matter damage in preterm mice.•Circ_19038 and lnc-AK016022 played a synergistic role.•Circ_19038/lnc-AK016022 increased Sirt1 expression by adsorbing miR-1b/miR-328.