title: Atrazine Causes Autophagy- and Apoptosis-Related Neurodegenerative Effects in Dopaminergic Neurons in the Rat Nigrostriatal Dopaminergic System.
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.
authors.affiliation: Department of Hygienic Toxicology, School of Public Health, Harbin Medical University, 157 Baojian Road, Nan Gang District, Harbin 150081, China. hedgehogviv@outlook.com.
authors.forename: Xiao-Yao
authors.initials: XY
authors.lastname: Song
authors.affiliation: Department of Hygienic Toxicology, School of Public Health, Harbin Medical University, 157 Baojian Road, Nan Gang District, Harbin 150081, China. love512133nan@163.com.
authors.forename: Jia-Nan
authors.initials: JN
authors.lastname: Li
authors.affiliation: Department of Hygienic Toxicology, School of Public Health, Harbin Medical University, 157 Baojian Road, Nan Gang District, Harbin 150081, China. Wuyanping_1964@aliyun.com.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Wu
authors.affiliation: Department of Hygienic Toxicology, School of Public Health, Harbin Medical University, 157 Baojian Road, Nan Gang District, Harbin 150081, China. sky_zhangbo_sea@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Hygienic Toxicology, School of Public Health, Harbin Medical University, 157 Baojian Road, Nan Gang District, Harbin 150081, China. libaix@ems.hrbmu.edu.cn.
authors.forename: Bai-Xiang
authors.initials: BX
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001280:Atrazine / Q000009:adverse effects / Q000633:toxicity*; D001343:Autophagy; D000071186:Beclin-1; D053453:Caspase 9 / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D006540:Herbicides / Q000009:adverse effects / Q000633:toxicity*; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D001280:Atrazine; D000071186:Beclin-1; D053453:Caspase 9; D006540:Herbicides; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat
keywords: apoptosis; atrazine; autophagy; dopaminergic neuron; neurotoxicity; wistar rats