title: Acute toluene exposure alters expression of genes in the central nervous system associated with synaptic structure and function.
abstract: 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 6 h. Specific brain regions were collected from the rats either immediately after 6 h of treatment or 18 h 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 showed 226 and 3352 transcripts altered in the toluene-exposed groups relative to controls at the 6 h time point and after the 18 h recovery period, respectively. Relative to controls, toluene exposure was associated with induction or repression of genes in pathways associated with synaptic plasticity, including long-term depression, GABA receptor signaling and mitochondrial function. In each of these pathways, responses were characterized by changes in a small number of transcripts following the 6 h toluene inhalation and with substantial increases in numbers of changed transcripts at 18 h recovery following termination of exposure. This report provides the first global genomic evidence that CNS pathways affected by toluene are strongly associated with neurological processes participating in synaptic transmission and plasticity.
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. hester.susan@epa.gov
authors.forename: Susan D
authors.initials: SD
authors.lastname: Hester
authors.forename: Andrew F M
authors.initials: AF
authors.lastname: Johnstone
authors.forename: William K
authors.initials: WK
authors.lastname: Boyes
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bushnell
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Shafer
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D008954:Models, Biological; D025341:Principal Component Analysis / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors; D014050:Toluene / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D014050:Toluene