Alterations in mRNA and protein expression of glutamate transporters in rat hippocampus after paraoxon exposure

Neurotoxicology. 2016 Dec:57:251-257. doi: 10.1016/j.neuro.2016.10.009. Epub 2016 Oct 18.

Abstract

Organophosphates affect brain function through a variety of mechanisms beyond their shared role as cholinesterase inhibitors. The aim of the current study was to investigate the changes in the expression of glial (GLAST and GLT-1) and neuronal (EAAC1) glutamate transporters at mRNA and protein levels in paraoxon-treated rat hippocampus. Adult male Wistar rats were intraperitoneally treated with either vehicle (corn oil) or one of three dosages of paraoxon (0.3, 0.7 or 1mg/kg). After 4 or 18h, both hippocampi of each rat were collected to detect mRNA and protein expression of glutamate transporters using the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. Animals treated with 0.3mg/kg paraoxon showed no difference in mRNA and protein levels of the glutamate transporters when compared with control group. At 4h after exposure with 0.7 and 1mg/kg paraoxon, the expression of GLAST and GLT-1 increased at mRNA and protein levels and remained elevated after 18h. No difference in the expression of EAAC1 at mRNA and protein levels was observed in any paraoxon-treated groups compared with the control group. This study showed an increased expression of glial (GLAST and GLT-1), but not neuronal (EAAC1) glutamate transporters, in adult rat hippocampus following administration of convulsive dosages of paraoxon. These suggest a protective and compensatory adaptation for effective uptake of glutamate in hippocampus induced by paraoxon and thus attenuating seizure activity.

Keywords: Glutamate transporter; Hippocampus; Paraoxon; mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Amino Acid Transport System X-AG / genetics*
  • Amino Acid Transport System X-AG / metabolism*
  • Analysis of Variance
  • Animals
  • Cholinesterase Inhibitors / toxicity*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Transporter 1 / genetics
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Excitatory Amino Acid Transporter 2 / genetics
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Gene Expression Regulation / drug effects*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Paraoxon / toxicity*
  • RNA, Messenger / metabolism
  • Radioimmunoprecipitation Assay
  • Rats
  • Rats, Wistar

Substances

  • Amino Acid Transport System X-AG
  • Cholinesterase Inhibitors
  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 2
  • RNA, Messenger
  • Slc1a2 protein, rat
  • Slc1a3 protein, rat
  • Acetylcholinesterase
  • Paraoxon