Chronic toluene exposure induces cell proliferation in the mice SVZ but not migration through the RMS.

Abuse of toluene-containing inhalants is associated to various cognitive impairments that have been partly associated to deviation of the hippocampal neurogenesis processes during adulthood. In the present study we analyzed the effect of chronic toluene exposure (6000ppm) on cell proliferation and migration in the other selected area of the rodent brain where neurogenesis persist throughout adulthood, the subventricular zone of the lateral ventricle (SVZ). We used an anti-Ki67 antibody to evaluate SVZ cell proliferation, BrdU to evaluate cell survival and double-staining with BrdU and the migration marker doublecortin (DCX) to evaluate migration, by immunofluorescence 2h, 1, 5, 10 or 15 days after 20 sessions of toluene exposure. We found that toluene induced an initial burst of cell proliferation in the SVZ but not a significant increase in migration toward the rostral migratory stream (RMS) or the number of cells that migrate to the olfactory bulb. In addition, we detected a small number of new migrating cells in the corpus callosum and striatum of control mice that was similar in toluene-exposed brains. These results may underline the homeostatic capabilities of the populations of dividing cells, previously demonstrated using other drugs of abuse and demonstrate that toluene misuse can alter cellular proliferation in the postnatal brain.

Toluene impairs learning and memory, has antinociceptive effects, and modifies histone acetylation in the dentate gyrus of adolescent and adult rats.

Toluene misuse usually initiates at an early age when the central nervous system is still immature, causing deleterious effects such as cognitive impairment. Epigenetic regulatory mechanisms have been proposed to explain long-term changes involved not only in memory, but also in toluene's actions. The aim of this study was to evaluate the effects of acute and chronic toluene exposure on learning, memory and histone acetylation in the rat hippocampus during two stages of life: adolescence and young adulthood. Because the memory tests used in this work involved object exploration and the perception of a noxious stimulus, general activity and nociception tests were also conducted. Acute and chronic toluene inhalation impaired learning, short-term and long-term memory in an object-recognition test and in an inhibitory avoidance task in both groups of age. This effect was concentration-dependent and occurred even at low toluene concentrations (1000, 2000 ppm) that were otherwise non-effective. Acute toluene inhalation produced antinociception, and tolerance to this effect developed after chronic exposure. Histone acetylation in the dentate gyrus showed differences depending on the histone, treatment and age: a single toluene exposure increased H4 acetylation in adolescents and young adult rats, whereas chronic exposure decreased H3 acetylation, but only in adults. In conclusion, this work provides evidence of toluene-induced impairment on learning, short- and long-term memory in adolescent and young adult rats, and shows that even a single toluene exposure can induce epigenetic modifications in the rat hippocampus.