Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations. (20th November 2017)

• Record Type: Journal Article
• Authors: Kaushik, Gaurav; Xia, Yu; Pfau, Jean C.; Thomas, Michael A.
• Is Part Of: Neuroscience letters. Volume 661(2017)
• Page Start: 143
• Page End: 148
• Publication Date: 2017-11-20
• Subjects: Psychoactive pharmaceuticals -- Environmental toxicology -- Drinking water -- Autism spectrum disorders (ASD); Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2017.09.058
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Psychoactive pharmaceuticals have been detected at low concentrations (in ppb) in wastewater, streams and drinking water. Autism-associated synaptic proteins were significantly altered by psychoactive pharmaceuticals at low concentrations. Psychoactive pharmaceuticals as environmental contaminants may contribute to the etiology of neurological disorders. Abstract: Autism Spectrum Disorders (ASD) are complex neurological disorders for which the prevalence in the U.S. is currently estimated to be 1 in 50 children. A majority of cases of idiopathic autism in children likely result from unknown environmental triggers in genetically susceptible individuals. These triggers may include maternal exposure of a developing embryo to environmentally relevant minute concentrations of psychoactive pharmaceuticals through ineffectively purified drinking water. Previous studies in our lab examined the extent to which gene sets associated with neuronal development were up- and down-regulated (enriched) in the brains of fathead minnows treated with psychoactive pharmaceuticals at environmental concentrations. The aim of this study was to determine whether similar treatments would alter in vitro expression of ASD-associated synaptic proteins on differentiated human neuronal cells. Human SK-N-SH neuroblastoma cells were differentiated for two weeks with 10μM retinoic acid (RA) and treated with environmentally relevant concentrations of fluoxetine, carbamazepine or venlafaxine, and flow cytometry technique was used to analyze expression of ASD-associated synaptic proteins. Data showed that carbamazepine individually, venlafaxine individually and mixture treatment at environmental concentrations significantly altered the expression of key synaptic proteins (NMDAR1, PSD95, SV2A, HTR1B, HTR2C and OXTR). Data indicated that psychoactive pharmaceuticals at extremely low concentrations altered the in vitro expression of key synaptic proteins that may potentially contribute to neurological disorders like ASD by disrupting neuronal development.