Iron deficiency in astrocytes alters cellular status and impacts on oligodendrocyte differentiation

IF 2.9 3区 医学 Q2 NEUROSCIENCES
María Silvina Marcora, Vanesa Soledad Mattera, Pilar Goñi, Florencia Aybar, Jorge Daniel Correale, Juana Maria Pasquini
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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 Fe3+ 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.

Abstract Image

星形胶质细胞缺铁会改变细胞状态并影响少突胶质细胞的分化
铁缺乏症(ID)已被证明会影响中枢神经系统(CNS)的发育并诱发髓鞘化不足。我们实验室之前在妊娠期缺铁性贫血模型中的研究表明,少突胶质细胞(OLG)和星形胶质细胞(AST)的成熟都受到了影响。为了探索 AST 铁对髓鞘化过程的贡献,我们通过沉默 AST 中的二价金属转运体 1(DMT1)(siDMT1 AST)或用 Fe3+ 螯合剂去铁胺(DFX;DFX AST)处理 AST,建立了一个体外 ID 模型。用 siDMT1 AST 与少突胶质细胞前体细胞(OPC)共培养,以及用 siDMT1 AST 条件培养基(ACM)培养少突胶质细胞前体细胞,均导致少突胶质细胞前体细胞成熟度降低。这些发现与 AST 分泌的因子 IGF-1、NRG-1 和 LIF 的表达减少有关,已知这些因子能促进 OPC 的分化。与对照细胞相比,siDMT1 AST 还显示线粒体数量增加、线粒体大小减小。DFX AST 也仍然不成熟,DFX AST 条件培养基也阻碍了培养中的 OPC 成熟,这与 AST 分泌的生长因子 IGF-1、NRG-1、LIF 和 CNTF 的表达减少是一致的。DFX AST线粒体形态和数量的结果与在 siDMT1 AST 中观察到的结果相似。总之,我们的结果表明,通过两种不同方法诱导的 ID 影响了 AST 的成熟和线粒体功能,进而阻碍了 OPC 的分化。
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来源期刊
Journal of Neuroscience Research
Journal of Neuroscience Research 医学-神经科学
CiteScore
9.50
自引率
2.40%
发文量
145
审稿时长
1 months
期刊介绍: The Journal of Neuroscience Research (JNR) publishes novel research results that will advance our understanding of the development, function and pathophysiology of the nervous system, using molecular, cellular, systems, and translational approaches. JNR covers both basic research and clinical aspects of neurology, neuropathology, psychiatry or psychology. The journal focuses on uncovering the intricacies of brain structure and function. Research published in JNR covers all species from invertebrates to humans, and the reports inform the readers about the function and organization of the nervous system, with emphasis on how disease modifies the function and organization.
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