Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms

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.