Atrazine Causes Autophagy- and Apoptosis-Related Neurodegenerative Effects in Dopaminergic Neurons in the Rat Nigrostriatal Dopaminergic System.

Xiao-Yao Song,Jia-Nan Li,Bai-Xiang Li,Yan-Ping Wu,Bo Zhang

doi:10.3390/ijms160613490

Xiao-Yao Song, Jia-Nan Li + Show 3 more

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https://doi.org/10.3390/ijms160613490

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Abstract

Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) is widely used as a broad-spectrum herbicide. Animal studies have demonstrated that ATR exposure can cause cell death in dopaminergic neurons. The molecular mechanisms underlying ATR-induced neuronal cell death, however, are unknown. In this study, we investigated the autophagy and apoptosis induced by ATR in dopaminergic neurons in vivo. Wistar rats were administered with ATR at doses of 10, 50 and 100 mg/kg body weight by oral gavage for three months. In terms of histopathology, the expression of autophagy- and apoptosis-related genes as well as proteins related to the Beclin-1/B-cell lymphoma 2 (Bcl-2) autophagy and apoptosis pathways were examined in the rat nigrostriatal dopaminergic system. We observed degenerative micromorphology indicative of neuronal apoptosis and mitochondrial autophagy by electron microscopy in ATR-exposed rat striatum. The rat ventral mesencephalon in the ATR-exposed groups also showed increased expression of Beclin-1, LC3-II, Bax and Caspase-9, and decreased expression of tyrosine hydroxylase (TH), Bcl-xl and Bcl-2. These findings indicate that ATR may induce autophagy- and apoptosis-related changes in doparminergic neurons. Furthermore, this induction may be regulated by the Beclin-1 and Bcl-2 autophagy and apoptosis pathways, and this may help to better understand the mechanism underlying the neurotoxicity of ATR.

Highlights

Atrazine (6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, ATR) is the most commonly used broad-spectrum herbicide in agricultural crops such as corn, sorghum, and sugarcane [1,2]. farm usage of ATR is regulated in the EU, ATR remains one of the most commonly used pesticides in the world, and it is continually detected in the ground water in the US, Italy and Greece [3,4,5,6]
We found that ATR induced autophagy- and apoptosis-related neurodegenerative effects on the dopaminergic neurons of adult male Wistar rats
These results indicated that ATR did not just affect the number of dopaminergic neurons, but that it inhibited the mRNA and protein expression of tyrosine hydroxylase (TH)

Summary

Introduction

Atrazine (6-chloro-N-ethyl-N′-(1-methylethyl)-1,3,5-triazine-2,4-diamine, ATR) is the most commonly used broad-spectrum herbicide in agricultural crops such as corn, sorghum, and sugarcane [1,2]. farm usage of ATR is regulated in the EU, ATR remains one of the most commonly used pesticides in the world, and it is continually detected in the ground water in the US, Italy and Greece [3,4,5,6]. According to a report by the European Union, residual ATR density decreased with increasing agricultural soil depth, it remained a significant environmental and biological hazard at the concentrations detected [12]. Due to their high and consistent ATR exposure, the health of farm workers and the residual metabolites that can be found in their urine is of particular concern [13]. Substantial levels of ATR and its metabolic products have been detected in urine samples from a farming community living within the proximity of herbicide use [14]. An increased incidence of Parkinson’s disease (PD) in agricultural workers in rural environments has been attributed to ATR exposure [15,16]

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