A study of the age-related effects of lactational atrazine exposure.
A growing number of reports have demonstrated that the widely-used herbicide Atrazine (ATR) can cause injury to dopamine (DA) neurons, but the exact mechanism remains unclear. In this study, we examined the effects of lactational ATR exposure in Sprague-Dawley rats on dopaminergic neuron health later in life. Compared with control rats, rats exposed to ATR during a critical period of neural development showed decreased striatal DA content and increased rates of DA turnover. The expression of Monoamine oxidase (MAO), which is associated with DA degradation, was up-regulated, and the expression of Vesicular Monoamine Transporter 2 (VMAT2), which is associated with DA transport, was down-regulated. The expression of transcription factor Nuclear Receptor Related Factor 1 (Nurr1), which is associated with DA neuron development, was down-regulated. Increased age (6-12 months old) increased the statistical significance of the differences of the above indicators in the ATR-treated rats compared to the control rats (P<0.05). Taken together, our results indicate that ATR exposure during the critical neural development period causes a down-regulation of Nurr1, which in turn affects Nurr1 target genes, including MAO, VMAT2 and DAT, which are involved in DA degradation and transport. Reduced expression of these genes impairs the capacity for vesicular storage or reuptake of DA, causing decreased levels of striatal DA, which can ultimately lead to DA neuron injury. DA neuron injuries become more severe over time, which suggests that aging can synergistically promote the ATR-associated DA neuron injuries.
Department of Toxicology, School of Public Health, Harbin Medical University, Harbin, 150081, China.
Yan
Y
Sun
Department of Toxicology, School of Public Health, Harbin Medical University, Harbin, 150081, China.
Yan-Shu
YS
Li
Department of Toxicology, School of Public Health, Harbin Medical University, Harbin, 150081, China.
Bai
B
Li
Department of Toxicology, School of Public Health, Harbin Medical University, Harbin, 150081, China.
Kun
K
Ma
Department of Toxicology, School of Public Health, Harbin Medical University, Harbin, 150081, China. Electronic address: libaixianghmu@aliyun.com.cn.
Bai-Xiang
BX
Li
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001280:Atrazine / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects*; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D006719:Homovanillic Acid / Q000378:metabolism; D007774:Lactation / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D006540:Herbicides; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D008995:Monoamine Oxidase; D001280:Atrazine; D004298:Dopamine; D006719:Homovanillic Acid
Atrazine; Developmental susceptibility; Dopaminergic metabolism pathway; Nuclear receptor related factor 1; Parkinson’s Disease