title: Psychoactive pharmaceuticals at environmental concentrations induce in vitro gene expression associated with neurological disorders.
abstract: A number of researchers have speculated that neurological disorders are mostly due to the interaction of common susceptibility genes with environmental, epigenetic and stochastic factors. Genetic factors such as mutations, insertions, deletions and copy number variations (CNVs) are responsible for only a small subset of cases, suggesting unknown environmental contaminants play a role in triggering neurological disorders like idiopathic autism. Psychoactive pharmaceuticals have been considered as potential environmental contaminants as they are detected in the drinking water at very low concentrations. Preliminary studies in our laboratory identified gene sets associated with neuronal systems and human neurological disorders that were significantly enriched after treating fish brains with psychoactive pharmaceuticals at environmental concentrations. These gene expression inductions were associated with changes in fish behavior. Here, we tested the hypothesis that similar treatments would alter in vitro gene expression associated with neurological disorders (including autism) in human neuronal cells. We differentiated and treated human SK-N-SH neuroblastoma cells with a mixture (fluoxetine, carbamazepine and venlafaxine) and valproate (used as a positive control to induce autism-associated profiles), followed by transcriptome analysis with RNA-Seq approach.
  
  
  
  We found that psychoactive pharmaceuticals and valproate significantly altered neuronal gene sets associated with human neurological disorders (including autism-associated sets). Moreover, we observed that altered expression profiles in human cells were similar to gene expression profiles previously identified in fish brains.
  
  
  
  Psychoactive pharmaceuticals at environmental concentrations altered in vitro gene expression profiles of neuronal growth, development and regulation. These expression patterns were associated with potential neurological disorders including autism, suggested psychoactive pharmaceuticals at environmental concentrations might mimic, aggravate, or induce neurological disorders.
authors.affiliation: Department of Biological Sciences, Idaho State University, Stop 8007, 921S 8th Ave, Pocatello, ID, 83209-8007, USA. gkaushik@ucdavis.edu.|Department of Medical Pathology and Laboratory Medicine, University of California at Davis, Davis, CA, 95817, USA. gkaushik@ucdavis.edu.|Present Address: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children, Northern California, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA. gkaushik@ucdavis.edu.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaushik
authors.affiliation: Division of Biological Sciences, University of Montana, 32 Campus Dr, Missoula, MT, 59812, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Biological Sciences, Idaho State University, Stop 8007, 921S 8th Ave, Pocatello, ID, 83209-8007, USA.
authors.forename: Luobin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biological Sciences, Idaho State University, Stop 8007, 921S 8th Ave, Pocatello, ID, 83209-8007, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Thomas
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics*; D002220:Carbamazepine / Q000506:poisoning; D045744:Cell Line, Tumor; D004785:Environmental Pollutants / Q000506:poisoning*; D005473:Fluoxetine / Q000506:poisoning; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D009422:Nervous System Diseases / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology; D011619:Psychotropic Drugs / Q000506:poisoning*; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics; D014635:Valproic Acid / Q000506:poisoning; D000069470:Venlafaxine Hydrochloride / Q000506:poisoning
chemical_list: D004785:Environmental Pollutants; D011619:Psychotropic Drugs; D005473:Fluoxetine; D002220:Carbamazepine; D014635:Valproic Acid; D000069470:Venlafaxine Hydrochloride