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Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations

Gaurav Kaushik1, Yu Xia2, Jean C Pfau3

  • 1Department of Biological Sciences, Idaho State University, Stop 8007, 921 S 8th Ave., Pocatello, ID 83209-8007, USA; Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53705 USA.

Neuroscience Letters
|October 3, 2017
PubMed

Insights

Environmental psychoactive pharmaceuticals in drinking water may impact child neurological development. This study found low concentrations alter key synaptic proteins in human neuronal cells, potentially contributing to Autism Spectrum Disorder (ASD).

Area of Science:

  • Neuroscience
  • Environmental Health
  • Developmental Biology

Background:

  • Autism Spectrum Disorder (ASD) affects 1 in 50 U.S. children, with environmental triggers suspected in genetically susceptible individuals.
  • Maternal exposure to psychoactive drugs in drinking water is a potential environmental trigger for ASD.
  • Previous research showed altered gene expression in fish brains exposed to pharmaceuticals.

Purpose of the Study:

  • To investigate if environmental concentrations of psychoactive pharmaceuticals alter Autism Spectrum Disorder (ASD)-associated synaptic protein expression in human neuronal cells.
  • To determine the in vitro effects of fluoxetine, carbamazepine, and venlafaxine on neuronal cells.

Main Methods:

  • Human SK-N-SH neuroblastoma cells were differentiated using retinoic acid (RA).
  • Cells were exposed to environmentally relevant concentrations of fluoxetine, carbamazepine, or venlafaxine.
  • Flow cytometry analyzed the expression of key synaptic proteins (NMDAR1, PSD95, SV2A, HTR1B, HTR2C, OXTR).

Main Results:

  • Carbamazepine, venlafaxine (individually), and their mixture significantly altered synaptic protein expression at environmental concentrations.
  • Specific proteins affected include NMDAR1, PSD95, SV2A, HTR1B, HTR2C, and OXTR.
  • Extremely low concentrations of these drugs impacted in vitro expression of critical synaptic proteins.

Conclusions:

  • Psychoactive pharmaceuticals at environmental concentrations can disrupt the expression of key synaptic proteins in human neuronal cells.
  • This disruption may contribute to neurological disorders like Autism Spectrum Disorder (ASD) by interfering with neuronal development.
  • Findings highlight the potential impact of contaminated drinking water on neurodevelopmental health.

Keywords:
Autism spectrum disorders (ASD)Drinking waterEnvironmental toxicologyPsychoactive pharmaceuticals

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