title: Acrylamide increases dopamine levels by affecting dopamine transport and metabolism related genes in the striatal dopaminergic system.
abstract: Dopaminergic system dysfunction is proved to be a possible mechanism in acrylamide (ACR) -induced neurotoxicity. The neurotransmitter dopamine (DA) has an increasingly important role in the dopaminergic system. Thus, the goal of this study is to evaluate effects of ACR on dopamine and its metabolite levels, dopamine transport and metabolic gene expression in dopaminergic neurons. Male Sprague-Dawley (SD) rats were dosed orally with ACR at 0 (saline), 20, 30, and 40 mg/kg/day for 20 days. Splayed hind limbs, reduced tail flick time and abnormal gait which preceded other neurologic parameters were observed in the above rats. ACR significantly increased dopamine levels, decreased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) contents in an area dependent manner in rat striatum. Immunohistochemical staining of the striatum revealed that the number of tyrosine hydroxylase (TH) positive cells significantly increased, while monoamine oxidase (MAO) positive cells were drastically reduced, which was consistent with changes in their mRNA and protein expressions. In addition, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) expression levels were both down-regulated in the striatum. These results suggest that dopamine levels increase significantly in response to ACR, presumably due to changes in the dopamine transport and metabolism related genes expression in the striatal dopaminergic neurons.
authors.affiliation: Department of Health Toxicology, MOE Key Lab of Environment Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Research institute for Environmental Medicine, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Pan
authors.affiliation: Shenzhen Luohu Institute of Health Inspection, Shenzhen 518000, China.
authors.forename: Xiongxiong
authors.initials: X
authors.lastname: Guo
authors.affiliation: Chongqing Jiulongpo Municipal Center for Disease and Prevention, Chongqing 400039, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.affiliation: Department of Health Toxicology, MOE Key Lab of Environment Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Guihong
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Research institute for Environmental Medicine, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Health Toxicology, MOE Key Lab of Environment Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yanhong@mails.tjmu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D020106:Acrylamide / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination; D005786:Gene Expression Regulation / Q000187:drug effects*; D006719:Homovanillic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493454:Slc18a2 protein, rat; C493216:Slc6a3 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D020106:Acrylamide; D004298:Dopamine; D006719:Homovanillic Acid
keywords: Acrylamide; DAT; Dopamine; MAO; TH; VMAT2