Multi-omics analysis reveals Mn exposure affects ferroptosis pathway in zebrafish brain

Area of Science:

• Neuroscience
• Toxicology
• Genomics

Background:

• Manganese (Mn) accumulation in the central nervous system can lead to neurotoxicity.
• The precise mechanisms underlying Mn-induced neurotoxicity are not fully understood.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms of Mn neurotoxicity using single-cell RNA sequencing (scRNA-seq) in zebrafish.
• To identify specific cell types and biological pathways affected by Mn exposure.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of zebrafish brain following Mn exposure.
• Identification of 10 distinct cell types, including dopaminergic (DA) neurons, using marker genes.
• Pseudotime analysis and joint multi-omics analysis (scRNA-seq and metabolomics).

Main Results:

• DA neurons were identified as critically involved in Mn-induced neurological damage.
• Chronic Mn exposure impaired amino acid and lipid metabolic processes in the brain.
• Mn exposure was found to disrupt the ferroptosis signaling pathway specifically in DA neurons.

Conclusions:

• Ferroptosis signaling pathway is a novel potential mechanism contributing to Mn neurotoxicity.
• scRNA-seq and multi-omics analysis provide valuable insights into Mn-induced brain damage at a single-cell level.