Toluene inhibits hippocampal neurogenesis in adult mice.

Toluene, a representative industrial solvent and abused inhalant, decreases neuronal activity in vitro and causes mental depression and cognitive impairment in humans. However, the effects of toluene on brain function and the sites of its action are poorly understood. This study investigated the temporal changes of neurogenesis in the hippocampus of adult C57BL/6 mice after acute administration of toluene using two immunohistochemical markers for neurogenesis, Ki-67 and doublecortin (DCX). In addition, after toluene treatment, depression-like behaviors and learning and memory tasks were examined to assess hippocampal neurogenesis-related behavioral dysfunction. The number of Ki-67- and DCX-positive cells in the dentate gyrus of adult hippocampi declined acutely between 0h and 24h after toluene treatment (500mg/kg, i.p.) and increased gradually from 2 to 8days post-administration. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of toluene administered (0–1000mg/kg). In tail suspension and forced-swim tests performed at 1 and 4days after toluene treatment (500mg/kg), mice showed significant depression-like behaviors compared to the vehicle-treated controls. In the contextual fear conditioning and object recognition memory test, the mice trained at 1 and 4days after toluene treatment showed significant memory defects compared to the vehicle-treated controls. This study suggests that acute exposure to toluene reduces the rate of adult hippocampal neurogenesis and can cause hippocampal dysfunction such as depression and cognitive impairment.