Session Title: Inflammation
STIMULATING SIGNALING PATHWAY LEADING TO CREB-MEDIATED TARGET GENE TRANSCRIPTION RELATED TO LEARNING AND MEMORY IN HIPPOCAMPUS OF TOLUENE-EXPOSED MICE
H. Fujimaki1, T.-T. Win-Shwe1, S. Yamamoto1, N. Kunugita2, K. Arashidani2
Exposure to organic solvents may be an important risk factor in induction of neurodegeneration associated with Parkinson's disease. However, these is no known mechanism by which organic solvents such as toluene may act to induce neurodegeneration. The role of D1 receptors in the maintenance of postsynaptic neurodegeneration was suggested. In this study, we investigated the effect of low-level toluene on expression of signaling pathway leading to CREB-mediated target gene in hippocampus of mice. Ten-week-old male C3H/HeN mice were exposed to 0, 5, 50, and 500 ppm toluene for 6 h per day, 5 days per week for 3 and 6 weeks in inhalation chamber. Because the individuals or animals with allergic inflammation are more sensitive to volatile organic solvent, animals were divided into two groups as non-allergy (NAG) group and allergy (AG) group. The AG groups were stimulated with ovalbumin (OVA) prior to toluene exposure. We examined D1, D2 and CREB-related genes in the mouse brain using real-time RT-PCR. The expression of D1 receptor mRNA in mice hippocampus was significantly increased in NAG group exposed to toluene. In AG groups, C3H/HeN mice showed significantly decreased D1 and D2 receptor mRNA expression in the hippocampus following toluene exposure for 3 weeks. However, exposure for 6 weeks enhanced the expression of D1 and D2 receptor as well as CREB1 mRNAs. As a consequence of enhanced signaling pathway leading to CREB-mediated target gene transcription, toluene may induce hyperreactivity in the hippocampus of mice.