Up-regulation of neurotrophin-related gene expression in mouse hippocampus following low-level toluene exposure

Abstract

To investigate the role of strain differences in sensitivity to low-level toluene exposure on neurotrophins and their receptor levels in the mouse hippocampus, 8-week-old male C3H/HeN, BALB/c and C57BL/10 mice were exposed to 0, 5, 50, or 500 ppm toluene for 6 h per day, 5 days per week for 6 weeks in an inhalation chamber. We examined the expressions of neurotrophin-related genes and receptors in the mouse hippocampus using real-time reverse transcription polymerase chain reaction (RT-PCR). The expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tyrosine kinase (Trk) A, and TrkB mRNAs in the C3H/HeN mice hippocampus was significantly higher in the mice exposed to 500 ppm toluene. Among the three strains of mice, the C3H/HeN mice seemed to be sensitive to toluene exposure. To examine the combined effect of toluene exposure and allergic challenge, the C3H/HeN mice stimulated with ovalbumin were exposed to toluene. The allergy group of C3H/HeN mice showed significantly elevated level of NGF mRNA in the hippocampus following exposure to 50 ppm toluene. Then, we also examined the expression of transcription factor, dopamine markers and oxidative stress marker in the hippocampus of sensitive strain C3H/HeN mice and found that the expression of CREB1 mRNA was significantly increased at 50 ppm toluene. In immunohistochemical analysis, the density of the NGF-immunoreactive signal was significantly stronger in the hippocampal CA3 region of the C3H/HeN mice exposed to 500 ppm toluene in non-allergy group and 50 ppm in allergy group. Our results indicate that low-level toluene exposure may induce up-regulation of neurotrophin-related gene expression in the mouse hippocampus depending on the mouse strain and an allergic stimulation in sensitive strain may decrease the threshold for sensitivity at lower exposure level.