去铁胺
少突胶质细胞
星形胶质细胞
DMT1型
细胞生物学
生物
化学
分子生物学
内分泌学
中枢神经系统
生物化学
运输机
髓鞘
基因
作者
María Silvina Marcora,Vanesa Soledad Mattera,Pilar Goñi,Florencia Aybar,Jorge Correale,Juana M. Pasquini
摘要
Abstract Iron deficiency (ID) has been shown to affect central nervous system (CNS) development and induce hypomyelination. Previous work from our laboratory in a gestational ID model showed that both oligodendrocyte (OLG) and astrocyte (AST) maturation was impaired. To explore the contribution of AST iron to the myelination process, we generated an in vitro ID model by silencing divalent metal transporter 1 (DMT1) in AST (siDMT1 AST) or treating AST with Fe 3+ chelator deferoxamine (DFX; DFX AST). siDMT1 AST showed no changes in proliferation but remained immature. Co‐cultures of oligodendrocyte precursors cells (OPC) with siDMT1 AST and OPC cultures incubated with siDMT1 AST‐conditioned media (ACM) rendered a reduction in OPC maturation. These findings correlated with a decrease in the expression of AST‐secreted factors IGF‐1, NRG‐1, and LIF, known to promote OPC differentiation. siDMT1 AST also displayed increased mitochondrial number and reduced mitochondrial size as compared to control cells. DFX AST also remained immature and DFX AST‐conditioned media also hampered OPC maturation in culture, in keeping with a decrease in the expression of AST‐secreted growth factors IGF‐1, NRG‐1, LIF, and CNTF. DFX AST mitochondrial morphology and number showed results similar to those observed in siDMT1 AST. In sum, our results show that ID, induced through two different methods, impacts AST maturation and mitochondrial functioning, which in turn hampers OPC differentiation.
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