Multi-Omics Analysis of Hippocampus in Rats Administered Trimethyltin Chloride

Abstract

Trimethyltin chloride (TMT) is a neurotoxicant that damages the central nervous system (CNS) and triggers neurodegeneration. This study used multi-omic data, including transcriptomics and proteomics of the rat hippocampus, to identify differentially expressed genes and proteins in TMT-induced neurotoxicity over time, related to neuro-axonal damage marked by plasma Neurofilament Light (NfL) levels. Data were collected at 12, 24, 48, 72, and 168 h post-TMT administration. NfL levels surged at 72 and 168 h, confirming neuro-axonal damage. Transcripts of genes in the chemokine signaling pathway (Cxcl10, Cxcl12, Cxcl14, Cxcl16), apoptosis pathway (Caspase-3, PARP1, CTSD), and TNF signaling pathway (TNFR1, MMP9, ICAM-1, TRAF3) showed significant differential expression starting from 48 h, preceding the NfL increase, suggesting their roles in neuro-axonal damage. Additionally, 11 Alzheimer’s disease-related proteins, with significant changes from 72 to 168 h, were detected only in the proteomic dataset, indicating post-translational modifications might be crucial in neurotoxicity. Pathway analysis revealed that neurodegeneration and Alzheimer’s disease pathways were among the top 15 affected by TMT-induced gene regulation, aligning with the involvement of TNF signaling, apoptosis, and chemokine signaling in neurodegeneration. This research highlighted the value of longitudinal omics studies, combined with pathway enrichment, gene-disease association, and neuro-axonal damage biomarker analyses, to elucidate neurotoxicant-induced neurodegeneration. Findings from this study could enhance the understanding of TMT-induced neurotoxicity, potentially informing future therapeutic strategies and preventive measures.