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

摘要

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 RNA5 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 alpha-synuclein (alpha-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/alpha-syn axis in the early stages of PD and can serve as a biomarker or therapeutic target for disease treatment. (C) 2019 Elsevier Ltd. All rights reserved.