Department of Radiation Biology & Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
Department of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
ACS Chem Neurosci. 2024 Sep 18;15(18):3311-3320. doi: 10.1021/acschemneuro.4c00231. Epub 2024 Aug 26.
In recent years, there has been a drastic surge in neurological disorders with sporadic cases contributing more than ever to their cause. Radiation exposure through diagnostic or therapeutic routes often results in neurological injuries that may lead to neurodegenerative pathogenesis. However, the underlying mechanisms regulating the neurological impact of exposure to near-low doses of ionizing radiation are not known. In particular, the neurological changes caused by metabolomic reprogramming have not yet been elucidated. Hence, in the present study, C57BL/6 mice were exposed to a single whole-body X-ray dose of 0.5 Gy, and 14 days post-treatment, the hippocampus was subjected to metabolomic analysis. The hippocampus of the irradiated animals showed significant alterations in 15 metabolites, which aligned with altered tyrosine, phenylalanine, and alpha-linolenic acid metabolism and the biosynthesis of unsaturated fatty acids. Furthermore, a multiomics interaction network comprising metabolomics and RNA sequencing data analysis provided insights into gene-metabolite interactions. Tyrosine metabolism was revealed to be the most altered, which was demonstrated by the interaction of several crucial genes and metabolites. The present study revealed the regulation of low-dose radiation-induced neurotoxicity at the metabolomic level and its implications for the pathogenesis of neurological disorders. The present study also provides novel insights into metabolomic pathways altered following near-low-dose IR exposure and its link with neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
近年来,神经系统疾病的发病率急剧上升,散发性病例比以往任何时候都对其病因有更多的贡献。通过诊断或治疗途径暴露于辐射会导致神经损伤,从而导致神经退行性发病机制。然而,调节暴露于近低剂量电离辐射对神经系统影响的潜在机制尚不清楚。特别是,代谢组学重编程引起的神经系统变化尚未阐明。因此,在本研究中,C57BL/6 小鼠接受单次全身 X 射线剂量 0.5 Gy,治疗后 14 天,对海马进行代谢组学分析。照射动物的海马体显示 15 种代谢物发生显著变化,与酪氨酸、苯丙氨酸和α-亚麻酸代谢以及不饱和脂肪酸的生物合成改变一致。此外,包含代谢组学和 RNA 测序数据分析的多组学相互作用网络提供了对基因-代谢物相互作用的深入了解。酪氨酸代谢被证明是最受影响的,这是由几个关键基因和代谢物的相互作用所证明的。本研究揭示了代谢组学水平上低剂量辐射诱导的神经毒性的调节及其对神经系统疾病发病机制的影响。本研究还提供了关于近低剂量 IR 暴露后改变的代谢途径及其与阿尔茨海默病和帕金森病等神经退行性疾病的联系的新见解。