The Effect of Exposure to Atrazine on Dopaminergic Development in Pubertal Male SD Rats

Birth Defects Res B Dev Reprod Toxicol. 2015 Oct;104(5):184-9. doi: 10.1002/bdrb.21151. Epub 2015 Sep 1.

Abstract

Atrazine (ATR, 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is used worldwide as a herbicide, and its presence in the environment has resulted in documented human exposure. A lack of strong evidence for genetic heritability of idiopathic Parkinson's disease has focused attention on environmental toxicants in the disease etiology, particularly agrichemicals. Parkinson's disease is associated with advanced age and is characterized by the degeneration of dopaminergic neurons, but it is unclear whether specific neuronal damage could result from insults during development. The juvenile period is particularly vulnerable to environmental agent, therefore, we evaluated the effects of a 28-day exposure to ATR on the dopaminergic system in pubertal rats. Sprague-Dawley rats were treated orally with ATR at 50, 100, and 200 mg/kg bw, daily from postnatal days 27 to 54. In this study, we examined the hypothesis that pubertal exposure to ATR would disrupt the development of the nigrostriatal dopamine (DA) system. The content of DA and levodopa (L-DA) were examined in striatum samples by HPLC-FL, and the mRNA and protein expression of tyrosine hydroxylase, orphan nuclear hormone receptor (Nurr1), Nurr1 interacting protein (NuIP), and cyclin-dependent kinase inhibitors of the Cip̲Kip family (p57kip2) were examined in samples of the nigrostriatum by use of fluorescence Real-Time quantitative polymerase chain reaction (PCR). Exposure of juvenile rats to the high dose of ATR led to reduced levels of DA and L-DA, genes expression of NuIP, Nurr1, and p57kip2 in animals.

Keywords: NuIP; Nurr1; atrazine; neurotoxicity; p57kip2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrazine / toxicity*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Environmental Exposure*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Levodopa / metabolism
  • Male
  • Maze Learning / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Sexual Maturation / drug effects*
  • Spatial Learning / drug effects
  • Swimming

Substances

  • RNA, Messenger
  • Levodopa
  • Atrazine
  • Dopamine