Manganese exposure during early larval stages of C. elegans causes learning disability in the adult stage

Manganese (Mn), even though an essential trace element, causes neurotoxicity in excess. In adults, over-exposure to Mn causes clinical manifestations, including dystonia, progressive bradykinesia, disturbance of gait, slurring, and stuttering of speech. These symptoms are mainly because of Mn-associated oxidative stress and degeneration of dopamine neurons in the central nervous system. Children with excessive Mn exposure often show learning disabilities but rarely show symptoms associated with dopaminergic neuron dysfunction. It is unclear why Mn exposure shows distinctive clinical outcomes in developing brains versus adult brains. Studies on nematode C. elegans have demonstrated that it is an excellent model to elucidate Mn-associated toxicity in the nervous system. In this study, we chronically exposed Mn to L1 larval stage of the worms to understand the effects on dopamine neurons and cognitive development. The worms showed modified behavior to exogenous dopamine compared to the control. The dopamine neurons showed resistance to neurodegeneration on repeated Mn exposure during the adult stage. As observed in mammalian systems, these worms showed significantly low olfactory adaptive learning and memory. This study shows that C. elegans alters adaptive developmental plasticity during Mn overexposure, modifying its sensitivity towards the metal ion and leads to remodeling in its innate learning behavior.