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Rao, B. S. S.

Publications and source records attributed to Rao, B. S. S..

2 recordsLinked to original sources

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

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 Alzheimers, Parkinsons, 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.

neuroscience↗

Low-dose exposure to malathion and radiation culminates in the dysregulation of multiple neuronal processes instigating neurotoxicity and activation of neurodegeneration pathways in mice hippocampus

Neurodegenerative disorders are a debilitating and persistent threat to the global elderly population carrying grim outcomes. Their genesis is often multifactorial, with a history of early exposure to xenobiotics like pesticides or diagnostic exposure to ionizing radiation. A holistic molecular insight into their mechanistic induction is still unclear upon single or combinatorial exposure to different toxicants. In the present study, one-month-old C57/BL-6J male mice were treated orally with malathion (MAL) (50mg/kg body wt. for 14 days) and/or a single whole-body radiation (IR) (0.5 Gy) on the 8th day. Post-treatment, behavioral assays were conducted to assess exploratory behavior, memory, and learning. Following sacrifice, brains were collected for histology, biochemical assays, and transcriptomic analysis. Differential expression analysis, Gene ontology, and pathway enrichment revealed several common and uniquely altered genes, biological processes, and pathways related to neurodegeneration, synaptic transmission and plasticity, neuronal survival, proliferation, and regulation of neuronal death. Increased astrogliosis was observed in the IR and co-exposure groups, with significant neuronal cell death and reduction in the expression of NeuN in all three groups. Sholl analysis and dendritic arborization/ spine density study revealed decreased total apical neuronal path length and dendritic spine density in all three groups. Decreased levels of antioxidant enzymes GST and GSH and acetylcholinesterase enzyme activity were also detected. However, there were no changes in exploratory behavior or learning and memory. Thus, explicating the molecular mechanisms behind MAL and IR can provide novel insights into the genesis of environmental factor-driven neurodegenerative pathogenesis.

neuroscience↗