Deciphering chemically-induced reversible neurotoxicity by reconstructing perturbed pathways from time series microarray gene expression data

Abstract

The etiology of chemically-induced neurotoxicity like seizures is poorly understood. Using reversible neurotoxicity induced by two neurotoxicants as example, we demonstrate that a bioinformatics-guided reverse engineering approach can be applied to analyze time series microarray gene expression data and uncover the underlying molecular mechanism. Our results reinforce previous findings that cholinergic and GABAergic synapse pathways are the target of carbaryl and RDX, respectively. We also conclude that perturbations to these pathways by sublethal concentrations of RDX and carbaryl were temporary, and earthworms were capable of fully recovering at the end of the 7-day recovery phase. In addition, our study indicates that many pathways other than those related to synaptic and neuronal activities were altered during the 6-day exposure phase.