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Int. J. Mol. Sci. 2015, 16(6), 13490-13506; doi:10.3390/ijms160613490

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

Department of Hygienic Toxicology, School of Public Health, Harbin Medical University, 157 Baojian Road, Nan Gang District, Harbin 150081, China
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Stephen C. Bondy
Received: 24 March 2015 / Revised: 30 May 2015 / Accepted: 2 June 2015 / Published: 12 June 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: atrazine; autophagy; apoptosis; neurotoxicity; wistar rats; dopaminergic neuron atrazine; autophagy; apoptosis; neurotoxicity; wistar rats; dopaminergic neuron
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Song, X.-Y.; Li, J.-N.; Wu, Y.-P.; Zhang, B.; Li, B.-X. Atrazine Causes Autophagy- and Apoptosis-Related Neurodegenerative Effects in Dopaminergic Neurons in the Rat Nigrostriatal Dopaminergic System. Int. J. Mol. Sci. 2015, 16, 13490-13506.

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