Exposure to atrazine during gestation and lactation periods: toxicity effects on dopaminergic neurons in offspring by downregulation of Nurr1 and VMAT2

Int J Mol Sci. 2014 Feb 18;15(2):2811-25. doi: 10.3390/ijms15022811.

Abstract

High atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) contents in the environment threaten the health conditions of organisms. We examined the effects of ATR exposure on Sprague-Dawley rats during gestation and on the dopaminergic neurons of offspring during lactation. Pregnant dams were orally treated with 0 mg/kg/day to 50 mg/kg/day of ATR from gestational day 5 to postnatal day 22. Afterward, neither offspring nor dams received ATR. Dopamine (DA) content was examined in striatum samples by HPLC-FL; the mRNA expressions of tyrosine hydroxylase (TH), orphan nuclear hormone (Nurr1), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) in the ventral midbrain samples were examined by fluorescence PCR when the offspring reached one year of age. After the pregnant rats were exposed to ATR, the DA concentrations and mRNA levels of Nurr1 were decreased in their offspring. Decreased Nurr1 levels were also accompanied by changes in the mRNA levels of VMAT2, which controls the transport and reuptake of DA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrazine / toxicity*
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / metabolism
  • Dopamine / analysis
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / metabolism
  • Down-Regulation / drug effects*
  • Female
  • Herbicides / toxicity*
  • Lactation
  • Male
  • Maternal Exposure / adverse effects
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / metabolism*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism
  • Vesicular Monoamine Transport Proteins / genetics
  • Vesicular Monoamine Transport Proteins / metabolism*

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Herbicides
  • Nr4a2 protein, rat
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • RNA, Messenger
  • Slc18a2 protein, rat
  • Vesicular Monoamine Transport Proteins
  • Tyrosine 3-Monooxygenase
  • Atrazine
  • Dopamine