Farrelly Lorna, Rosato-Siri Maria Victoria, Föcking Melanie, Codagnone Martin, Reines Analia, Dicker Patrick, Wynne Kieran, Farrell Michael, Cannon Mary, Cagney Gerard, Pasquini Juana Maria, Cotter David R
Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Department of Biological Chemistry, IQUIFIB, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Proteomics. 2017 Sep;17(17-18). doi: 10.1002/pmic.201600407.
Prenatal iron deficiency (pID) has been described to increase the risk for neurodevelopmental disorders such as autism and schizophrenia; however, the precise molecular mechanisms are still unknown. Here, we utilized high-throughput MS to examine the proteomic effects of pID in adulthood on the rat frontal cortex area (FCA). In addition, the FCA proteome was examined in adulthood following risperidone treatment in adolescence to see if these effects could be prevented. We identified 1501 proteins of which 100 were significantly differentially expressed in the FCA at postnatal day 90. Pathway analysis of proteins affected by pID revealed changes in metabolic processes, including the tricyclic acid cycle, mitochondrial dysfunction, and P13K/Akt signaling. Interestingly, most of these protein changes were not present in the adult pID offspring who received risperidone in adolescence. Considering the link between pID and several neurodevelopmental disorders such as autism and schizophrenia these presented results bring new perspectives to understand the role of iron in metabolic pathways and provide novel biomarkers for future studies of pID.
产前缺铁（pID）已被证实会增加患自闭症和精神分裂症等神经发育障碍的风险；然而，确切的分子机制仍不清楚。在此，我们利用高通量质谱技术研究成年大鼠前额叶皮质区域（FCA）中pID的蛋白质组学效应。此外，还研究了青春期接受利培酮治疗的成年大鼠的FCA蛋白质组，以观察这些效应是否可以预防。我们鉴定出1501种蛋白质，其中100种在出生后第90天的FCA中显著差异表达。对受pID影响的蛋白质进行的通路分析显示，代谢过程发生了变化，包括三羧酸循环、线粒体功能障碍和P13K/Akt信号传导。有趣的是，在青春期接受利培酮治疗的成年pID后代中，这些蛋白质变化大多不存在。鉴于pID与自闭症和精神分裂症等几种神经发育障碍之间的联系，这些研究结果为理解铁在代谢途径中的作用带来了新的视角，并为未来pID的研究提供了新的生物标志物。
