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

• Published in: International journal of molecular sciences 2015-06, Vol.16 (6), p.13490-13506
• Main Authors: Song, Xiao-Yao, Li, Jia-Nan, Wu, Yan-Ping, Zhang, Bo, Li, Bai-Xiang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis Regulatory Proteins - metabolism; atrazine; Atrazine - adverse effects; Atrazine - toxicity; Autophagy; bcl-2-Associated X Protein - metabolism; Beclin-1; Caspase 9 - metabolism; Dopamine; dopaminergic neuron; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Drug therapy; Herbicides - adverse effects; Herbicides - toxicity; Male; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - metabolism; Mesencephalon - ultrastructure; Microtubule-Associated Proteins - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; Neurodegeneration; Neurons; neurotoxicity; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Wistar; Rodents; wistar rats
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms160613490

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.