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Acute Toluene Exposure alters expression of genes associated with synaptic structure and function
Citation:
HESTER, S. D., A. Johnstone, W. K. BOYES, P. J. BUSHNELL, AND T. J. SHAFER. Acute Toluene Exposure alters expression of genes associated with synaptic structure and function. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
results show that TOL alters transcription of proteins in pathways associated with synaptic structure and function, and are consistent with previously-known effects of TOL on ion channels and synaptic transmission. (This abstract does not reflect EPA policy
Description:
Toluene (TOL), a volatile organic compound, is a ubiquitous air pollutant of interest to EPA regulatory programs. Whereas its acute functional effects are well described, several potential modes of action in the CNS have been proposed. Therefore, the genomic response to acute TOL exposure was investigated in rat CNS to investigate further the potential pathways mediating its acute neurological effects. Adult male Long-Evans rats inhaled clean air or 1000 ppm of TOL vapor for 6 hrs. Brains were collected either zero or 18 hrs after removal from the exposure chambers (n=6 / group / time). Total mRNA was extracted from the striatum of each brain and hybridized to Rat 230A Affymetrix arrays. Statistical analyses using ANOYA + FDR .05 showed 226 and 3352 genes altered in the TOL-exposed groups relative to controls at the 0-and 18-hr times, respectively. Relative to controls, a common set of genes 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. Analysis of the response at 0 hr showed differential effects of TOL on expression of transcripts for calcium and potassium channel subunits, induction of genes for early growth response (Egr2, involved in the onset of myelination) and GABA-ergic neurotransmission. The signature at 18 hrs showed marked effects on transcripts associated with synaptogenesis, EphrinB receptors (associated with dendritic spine morphogenesis), and GABA-receptor life cycling. These results provide evidence that genomic responses begin during 6 hrs of TOL inhalation and are enhanced 18 hrs later. These results show that TOL alters transcription of proteins in pathways associated with synaptic structure and function, and are consistent with previously-known effects of TOL on ion channels and synaptic transmission. (This abstract does not reflect EPA policy