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首页> 外文期刊>American Journal of Physiology >Gestational-neonatal iron deficiency suppresses and iron treatment reactivates IGF signaling in developing rat hippocampus
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Gestational-neonatal iron deficiency suppresses and iron treatment reactivates IGF signaling in developing rat hippocampus

机译：妊娠期新生婴儿铁缺乏症得到抑制，铁治疗重新激活了发育中的大鼠海马中的IGF信号

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Gestational- neonatal iron deficiency, a common micronutrient deficiency affecting the offspring of more than 30% of pregnancies worldwide, leads to long-term cognitive and behavioral abnormalities. Preclinical models of gestational-neonatal iron deficiency result in reduced energy me- tabolism and expression of genes critical for neuronal plasticity and cognitive function, which are associated with a smaller hippocampal volume and abnormal neuronal dendrite growth. Because insulin-like growth factor (IGF) modulates early postnatal cellular growth, differentiation, and survival, we used a dietary-induced rat model to assess the effects of gestational iron deficiency on activity of the IGF system. We hypothesized that gestational iron deficiency attenuates postnatal hippocampal IGF signaling and results in downstream effects that contribute to hippocampal anatomic and functional deficits. At postnatal day (P) 75 untreated gestational-neonatal iron deficiency markedly suppressed hippocampal IGF activation and protein kinase B signaling, and reduced neurogenesis, while elevating extracellular signal-regulated kinase 1/2 signaling and hypoxia-inducible factor-la expression. Iron treatment beginning at P7 restored IGF signaling, increased neurogenesis, and normalized all parameters by the end of rapid hippocampal differentiation (P30). Expression of the neuron-specific synaptogenesis marker, disc-large homolog 4 (PSD95), increased more rapidly than the glia-specific myelination marker, myelin basic protein, following iron treatment, suggesting a more robust response to iron therapy in IGF-I-dependent neurons than IGF-II-dependent glia. Collectively, our findings suggest that IGF dysfunction is in part responsible for hippocampal abnormalities in untreated iron deficiency. Early postnatal iron treatment of gestational iron deficiency reactivates the IGF system and promotes neurogenesis and differentiation in the hippocampus during a critical developmental period.
机译：妊娠期新生儿铁缺乏症是一种常见的微量营养素缺乏症，影响全球超过30％的孕妇的后代，导致长期的认知和行为异常。妊娠-新生儿铁缺乏症的临床前模型导致能量代谢减少以及对神经元可塑性和认知功能至关重要的基因的表达，这与较小的海马体积和异常的神经元树突生长有关。因为胰岛素样生长因子（IGF）调节出生后早期细胞的生长，分化和存活，所以我们使用饮食诱导的大鼠模型来评估妊娠期铁缺乏对IGF系统活性的影响。我们假设妊娠期铁缺乏会减弱出生后海马IGF信号传导，并导致下游效应，导致海马解剖和功能缺陷。在出生后第75天，未经治疗的妊娠-新生儿缺铁明显抑制了海马IGF激活和蛋白激酶B信号传导，并减少了神经发生，同时提高了细胞外信号调节激酶1/2信号传导和缺氧诱导的因子-1a表达。从P7开始的铁治疗可恢复IGF信号传导，增加神经发生并在海马快速分化（P30）结束之前使所有参数正常化。铁处理后，神经元特异性突触标记物，盘状大同系物4（PSD95）的表达比神经胶质特异性髓鞘标记物，髓鞘碱性蛋白的表达增加更快，这表明在IGF-I依赖神经元比依赖IGF-II的神经胶质细胞。总体而言，我们的发现表明，IGF功能障碍是造成未经治疗的铁缺乏症海马异常的部分原因。妊娠期铁缺乏症的早期产后铁疗法可在关键的发育时期重新激活IGF系统并促进海马神经发生和分化。

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