A single nucleotide polymorphism that affects oligodendroglial lineage cells may augment the consequences of neurotoxicants.

An increasing number of toxicants are found to target oligodendroglia lineage cells. Among them, environmental lead and oral alcohol reduce oligodendrogenesis and affect oligodendrocyte precursor cells (OPCs). OPCs perform a multitude of functions within the neuronal synaptic space and serve as progenitors to myelin capable oligodendrocytes. Aberrant OPCs result in neurobehavioral deficits in humans. A single nucleotide polymorphism (SNP) for the gene encoding the lysosomal enzyme arylsulfatase A (ASA) causes reduced cellular levels of the enzyme and potentially affects OPC homeostasis. A contributing, but not sole mechanism for toxicant-induced neurological damage is that the agent could cause reduced levels of ASA in OPCs. Individuals homozygous with this SNP may be predisposed to neurobehavioral symptoms of ethanol and lead exposure due to the ability of the toxicants to further reduce levels of ASA in OPCs. This SNP is found in high frequency in some ethnic populations and significant differences may be expected for the impact of relevant environmental toxicants on distinct exposed populations. Understanding the mechanisms of the environment-ARSA gene interaction and how neurotoxicants affect OPCs will facilitate the diagnosis of individuals exposed to the toxicants, as well as the development of therapeutics that minimize the effects of environmental neurotoxicants.