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Toluene Effects on Gene Expression in the Hippocampus of Young-Adult, Middle-Age and Senescent Brown Norway Rats
Citation:
ROYLAND, J. E., PRASADA RAO S. KODAVANTI, J. Schmid, AND R. C. MACPHAIL. Toluene Effects on Gene Expression in the Hippocampus of Young-Adult, Middle-Age and Senescent Brown Norway Rats. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 126(1):193-212, (2012).
Impact/Purpose:
We examined the effects of toluene, a known neurotoxicant with reported behavioral, electrophysiological and pathological effects, on transcriptomic changes in the rat brain at three different life stages in order to elucidate key molecular pathways responsible for toluene-induced neurotoxicity and its interaction with aging
Description:
Differential susceptibility to environmental exposure(s) across life stages is an area of toxicology about which little is known. We examined the effects of toluene, a known neurotoxicant with reported behavioral, electrophysiological and pathological effects, on transcriptomic changes in the rat brain at three different life stages in order to elucidate key molecular pathways responsible for toluene-induced neurotoxicity and its interaction with aging. Global genomic changes following acute oral toluene (0, 0.65 and 1.0 g/kg) were examined 4 hours after exposure in hippocampi of Brown Norway Rats at 4, 12 and 24 months of age. Data were analyzed by 2-way ANOVA to identify the effects of age, toluene and interactions between the 2 factors. A nested I-way ANOVA analysis and filtering on fold change (1.25x) identified 183 genes whose expression changed with age. The majority of the genes were up-regulated between life stages (>79%). Similar analysis for toluene-related genes found only 2 sequences to vary with dose. Fifty-six genes were identified by 2-way ANOVA to have expression changes due to an interaction between toluene and age. Expression of genes with roles in immune response, cytoskeleton, protein and energy metabolism was changed with advancing life stage, indicating changes in basic cellular homeostasis. Toluene affected similar cell functions, enhancing the effects of aging. The data indicate that life stage can impact of acute toluene exposure in various and complex ways, highlighting the need for further investigation into the role of aging in susceptibility to neurotoxicants.
