[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

Identification of miRNA-7 as a regulator of brain-derived neurotrophic factor/α-synuclein axis in atrazine-induced Parkinson's disease by peripheral blood and brain microRNA profiling

Chemosphere. 2019 Oct:233:542-548. doi: 10.1016/j.chemosphere.2019.05.064. Epub 2019 May 23.

Abstract

Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine; ATR) is widely used as an herbicide, and its accumulation in the environment is a health risk to humans; for instance, it has been shown to cause dopaminergic neurotoxicity. MicroRNAs (miRNAs) are endogenous small RNAs that regulate gene expression in diverse physiological contexts; however, the extent of their involvement in the development of Parkinson's disease (PD) is not known. In this study, we carried out miRNA profiling of peripheral blood and brain tissue in a rat model of PD in order to identify factors that mediate PD pathogenesis. The miRNAmiR-7 is known to cause the downregulation of α-synuclein (α-syn), which is linked to the neuropathology of PD. Here we found that miR-7 was upregulated in brain tissue but downregulated in peripheral blood of rats with ATR-induced PD. We also found that miR-7 regulates the expression of brain-derived neurotrophic factor (BDNF) through an auto regulatory mechanism. These findings indicate that miRNA-7 regulates the BDNF/α-syn axis in the early stages of PD and can serve as a biomarker or therapeutic target for disease treatment.

Keywords: Atrazine; BDNF; Parkinson’Disease; microRNA.

MeSH terms

  • Animals
  • Atrazine / toxicity*
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Dopamine / metabolism
  • Down-Regulation
  • Gene Expression
  • Gene Expression Regulation
  • Herbicides / toxicity*
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / genetics
  • Parkinson Disease, Secondary / metabolism*
  • Rats
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • Herbicides
  • MicroRNAs
  • alpha-Synuclein
  • BDNF protein, human
  • Atrazine
  • Dopamine