The SIRT1-ΔExon8 transcript is differentially expressed across brain regions and during neural stem cell differentiation in rats

Abstract

SIRT1 is an NAD+-dependent deacetylase involved in the maintenance and differentiation of neural stem cells (NSCs). Although alternative splicing increases the regulatory complexity of SIRT1, its splice isoforms in the rat nervous system remain poorly defined. This study aimed to identify SIRT1-ΔExon8 in rats, characterize its regional expression, and assess its association with NSC differentiation. Conventional PCR and qRT-PCR were used to examine SIRT1-FL and SIRT1-ΔExon8 mRNA expression in the rat hippocampus and cortex. Rat NSCs were cultured and induced to differentiate in vitro. Immunocytochemical staining was performed to verify differentiation, and total SIRT1 deacetylase activity was measured. SIRT1-ΔExon8 was identified in the rat nervous system at the transcriptional level. Its expression was markedly lower than that of SIRT1-FL in both the hippocampus and cortex and differed between these two regions. During NSC differentiation, SIRT1-FL expression increased together with total SIRT1 deacetylase activity, whereas SIRT1-ΔExon8 expression decreased. SIRT1-ΔExon8 is a rat SIRT1 splice isoform showing differential transcriptional expression across brain regions and during NSC differentiation. The opposite expression patterns of SIRT1-FL and SIRT1-ΔExon8 suggest that SIRT1 alternative splicing is associated with NSC differentiation in rats. Protein-level and functional studies are still needed to clarify the biological significance of SIRT1-ΔExon8.