Deciphering the Metabolic Shifts in The Hippocampus of Mice Subjected to Near Low Dose Radiation: Insights from Metabolomics and Integrated Multi-omics

Abstract

Recent years have witnessed a drastic upsurge 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 indicative of neurodegenerative pathogenesis. Nevertheless, the impact of low doses of radiation on the brain remains a subject of extensive discussion, as research findings have presented conflicting evidence regarding potential harm and benefits. In the present study, C57/BL mice were exposed to a whole-body single dose of 0.5 Gy X-ray. Fourteen days after treatment, the animals were euthanized, and the hippocampus was isolated and processed for metabolomic analysis. Statistical and bioinformatic analysis revealed 115 metabolites altered in the radiation-exposed group, while pathway enrichment analysis unveiled alterations in tyrosine, phenylalanine, aminoacyl-tRNA metabolism, arginine biosynthesis, glutathione, arginine, proline metabolism, etc. Furthermore, a multiomics interaction network of the genes and the metabolites was constructed to gather an overview of their interaction with the neighboring genes and metabolites in different pathways. These metabolic pathways correlate with synthesizing neurotransmitters such as dopamine and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and dementia. The present study findings unveiled metabolomic level regulation of low-dose radiation-induced neurotoxicity and its implication in the pathogenesis of neurological disorders.