Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms
Andrew Shaw, Jeffery D. Steketee, Anna N. Bukiya, Alex M. Dopico
Abstract
Toluene intoxication constitutes a persistent public health problem worldwide. While most organs can be damaged, the brain is a primary target whether exposure is accidental, occupational, or recreational. Interventions to prevent/revert brain damage by toluene are curtailed by the scarce information on the molecular targets and mechanisms mediating toluene's brain toxicity and the common exposure to other neurotoxins and/or coexistence of neurological/psychiatric disorders. We examine ( a ) the physicochemical properties of toluene that allow this inhalant to primarily target the lipid-rich brain; ( b ) the cell types targeted by toluene (neurons, different types of glia), while considering a cerebrovascular component; and ( c ) putative molecular mechanisms by which toluene may modify receptor function while analyzing structural features that allow toluene to directly interact with membrane lipids or specific proteins. This information constitutes a stepping stone to design pharmacotherapies that counteract toluene brain intoxication.