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Acute Toluene Exposure Alters Expression of Genes in the Central Nervous System Associated With Synaptic Structure and Function
Citation:
HESTER, S. D., A. F. JOHNSTONE, W. K. BOYES, P. J. BUSHNELL, AND T. J. SHAFER. Acute Toluene Exposure Alters Expression of Genes in the Central Nervous System Associated With Synaptic Structure and Function. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, 33(5):521-9, (2011).
Impact/Purpose:
This report provides the first global genomic evidence that pathways affected by toluene are strongly associated with neurological processes participating in synaptic plasticity.
Description:
Toluene is a volatile organic compound (VOC) and a ubiquitous air pollutant of interest to EPA regulatory programs. Whereas its acute functional effects are well described, several modes of action in the CNS have been proposed. Therefore, we sought to identify potential pathways mediating direct or indirect effects of VOCs by investigating the genomic response of the rat CNS to acutely-inhaled toluene. Adult male Long-Evans rats inhaled clean air or 1000 ppm toluene vapor for 6hr. Specific brain regions were collected from the rats after either 6hr of treatment or 18hr after removal from the exposure chambers (n=6/group/time). Total mRNA was extracted from the striatum and hybridized to Rat 230A Affymetrix arrays. Statistical analyses using ANOVA + False Discovery Rate (FDR) of 0.05 showed 226 and 3352 genes altered in the toluene-exposed groups relative to controls at the 6 and 18hr times, respectively. Relative to controls, a common set ofgenes was differentially expressed at both time-points, including genes for scaffold proteins that couple NMDA receptors to metabotrophic glutamate receptors and genes in pathways associated with long-term potentiation. The response at 6hr showed differential effects oftoluene on expression of transcripts for calcium and potassium channel subunits, induction of genes for early growth response (Egr2, involved in the onset ofmyelination) and GABA-ergic neurotransmission. In contrast, the signature at 18hr showed marked effects on transcripts associated with synaptogenesis, EphrinB receptors (associated with dendritic spine morphogenesis), and GABA-receptor life cycling. There was also evidence of transcriptional responses that begin during the 6hr of toluene inhalation which are enhanced 18hr following termination of exposure. This report provides the first global genomic evidence that pathways affected by toluene are strongly associated with neurological processes participating in synaptic plasticity
