Cortex metabolome and proteome analysis reveals chronic arsenic exposure via drinking water induces developmental neurotoxicity through hnRNP L mediated mitochondrial dysfunction in male rats

Lots of people are at the risk of arsenic-contaminated drinking water. Arsenic exposure was confirmed to be closely linked to neurocognitive deficits, particularly during childhood. The multi-omics approaches are known be well suitable for toxicological research. Thus, this study aimed to explore the molecular mechanisms of arsenic-induced learning and memory function impairments through the integrative proteome and metabolome analysis of cortex in rats. The weaned rats were exposed to arsenic-contaminated drinking water for six months to mimic the developmental exposure. 220 differential proteins and 19 differential metabolites were identified in the cortex, and nine potential biomarkers were found to be related to impaired Morris water maze (MWM) indicators. Chronic arsenic exposure affected the cognitive function by inducing the overproduction of amyloid-β (Aβ) peptides and the redox imbalance in the mitochondria. Glycolysis and tricarboxylic acid (TCA) cycle enhancement driven by the increased heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a low-dose protective mechanism against arsenic-induced ATP deficiency and oxidative stress. Moreover, apoptosis is another important pathway of arsenic-induced neurotoxicity. This study provides new evidence about the alterations of proteins and metabolites in the cortex of the exposed rats under arsenic toxicity. These findings suggest hnRNP L could be a potential target for the treatment of arsenic-induced neurotoxicity. [Display omitted] •Water borne arsenic exposure disrupted cortex proteome and metabolome in rats.•The increase of hnRNP L drove the arsenic-induced mitochondrial dysfunction.•Increased proteins in glycolysis and TCA cycle might protect against arsenic-induced ATP deficiency and oxidative stress.