Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat

Rodríguez, Verónica; Limón-Pacheco, Jorge H.; Mendoza-Trejo, M.S.; González‐Gallardo, Adriana; Hernández-Plata, Isela; Giordano, Magda

doi:10.1016/j.neuro.2012.10.012

Cited by 56 publications

(51 citation statements)

References 45 publications

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“…As hormones play a major role in the development of the central nervous system (CNS), recent research has suggested that ATR is a dopaminergic system toxicant. Exposure to 10 mg/kg bodyweight (BW) of ATR for 1 year was found to decrease dopamine concentrations in the striatum of male Sprague–Dawley (SD) rats [8], similar to that obtained in Albino rats intraperitoneally injected with a higher dose of ATR at 100 mg/kg BW [9]. In contrast, an increase in striatal dopamine and dopamine turnover were detected after acute oral exposure of C57BL/6 mice to ATR at 125 mg/kg BW [10].…”

Section: Introductionmentioning

confidence: 70%

“…The widespread application of ATR and its persistent existence in the environment have continued to gain extensive attention. Numerous recent reports have highlighted the adverse effects of ATR exposure on the CNS [8,9,10,11]. The developmental phase is a key period of constructing brain function, including learning and memory [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that ATR is a dopaminergic system toxicant, especially to dopamine in the striatum [8,9,10,15]. There is a strong relationship between dopamine content and hippocampal function, although the hippocampus is not a classic projective area of dopaminergic neurons.…”

Section: Discussionmentioning

confidence: 99%

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Developmental Exposure to Atrazine Impairs Spatial Memory and Downregulates the Hippocampal D1 Dopamine Receptor and cAMP-Dependent Signaling Pathway in Rats

et al. 2018

IJMS

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Atrazine (ATR) is a widely used herbicide that has been implicated as a neurotoxicant. Recent experimental evidence has implicated that ATR exposure also appears to have adverse effects on the hippocampus, which is a critical region for learning and memory. The aim of the present study was to investigate the effects of ATR toxicity on the hippocampus of developing rats. Postnatal day (PND) 28 male Sprague–Dawley (SD) rats received ATR by oral gavage at 10 or 100 mg/kg bodyweight (BW) for 30 consecutive days and were sacrificed at PND 90. Behavioral test results indicated that spatial learning and memory were affected by ATR treatment. Electron microscopy analysis showed that the ultrastructures of the hippocampus were altered in the ATR-treated groups, as compared to the control group. Additionally, ATR treatment impacted dopamine and D1 dopamine receptor (D1DR) contents through different mechanisms. Reduced mRNA and protein expression levels of factors involved in the cAMP-dependent signaling pathway were also detected. These results indicate that the developmental exposure of rats to ATR can damage the hippocampus and spatial memory, which might be related to the downregulation of expression levels of the D1DR and its downstream signaling pathway.

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Section: Introductionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Developmental Exposure to Atrazine Impairs Spatial Memory and Downregulates the Hippocampal D1 Dopamine Receptor and cAMP-Dependent Signaling Pathway in Rats

et al. 2018

IJMS

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“…In terms of its nervous system toxicity, ATR decreases the level of striatal dopamine (DA) and the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons in rodents, resulting in pathology and behavior similar to that of a Parkinson’s disease (PD) model. Epidemiological evidence suggests that rural farmers have a higher incidence of PD with high and consistent herbicide exposure [18-23]. …”

Section: Introductionmentioning

confidence: 99%

Isoflavones Induce BEX2-Dependent Autophagy to Prevent ATR-Induced Neurotoxicity in SH-SY5Y Cells

Ma¹,

Wu²,

Wu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Atrazine (ATR) is a broad-spectrum herbicide in wide use around the world. However, ATR is neurotoxic and can cause cell death in dopaminergic neurons, leading to neurodegenerative disorders. Autophagy is the basic cellular catabolic process involving the degradation of proteins and damaged organelles. Studies have shown that certain plant compounds can induce autophagy and prevent neuronal cell death. This prompted us to investigate plant compounds that might reduce the neurotoxic effects of ATR. Methods: By CCK-8 and flow cytometry, we tested the ability of five candidate compounds—isoflavones, resveratrol, quercetin, curcumin, and green tea polyphenols—to protect cells from ATR. Changes in the expression of tyrosine hydroxylase (TH) and brain-expressed X-linked 2 (BEX2), autophagy-related proteins and key factors in mTOR signaling, were detected by Western blotting. Results: Isoflavones had the strongest activity against ATR-induced neuronal apoptosis. ATR reduced the expression of TH and BEX2, whereas isoflavones increased TH and BEX2 expression. In addition, ATR inhibited autophagy, whereas isoflavones induced autophagy through the accumulation of LC3-II and decreased expression of p62; this effect was abolished by 3-methyladenine (3-MA). Furthermore, BEX2 siRNA abolished isoflavone-mediated autophagy and neuroprotection in vitro. Conclusion: Isoflavones activate BEX2-dependent autophagy, protecting against ATR-induced neuronal apoptosis.

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“…Multiple studies have started to examine the effects of atrazine on the dopaminergic system caused by developmental and adulthood exposures (Coban and Filipov, 2007; Lin et al 2013a; Rodriguez et al 2013). However, the effect of atrazine on other monoamine neurotransmitters such as serotonin (5-HT), as well as its effects on the GABAergic system is still under investigation (Das et al 2000; Rajkovic et al 2011).…”

Section: 0 Introductionmentioning

confidence: 99%

Developmental origins of neurotransmitter and transcriptome alterations in adult female zebrafish exposed to atrazine during embryogenesis

et al. 2015

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Atrazine is an herbicide applied to agricultural crops and is indicated to be an endocrine disruptor. Atrazine is frequently found to contaminate potable water supplies above the maximum contaminant level of 3 µg/L as defined by the U. S. Environmental Protection Agency. The developmental origin of adult disease hypothesis suggests that toxicant exposure during development can increase the risk of certain diseases during adulthood. However, the molecular mechanisms underlying disease progression are still unknown. In this study, zebrafish embryos were exposed to 0, 0.3, 3, or 30 µg/L atrazine throughout embryogenesis. Larvae were then allowed to mature under normal laboratory conditions with no further chemical treatment until 7 days post fertilization (dpf) or adulthood and neurotransmitter analysis completed. No significant alterations in neurotransmitter levels was observed at 7 dpf or in adult males, but a significant decrease in 5-Hydroxyindoleacetic acid (5-HIAA) and serotonin turnover was seen in adult female brain tissue. Transcriptomic analysis was completed on adult female brain tissue to identify molecular pathways underlying the observed neurological alterations. Altered expression of 1853, 84, and 419 genes in the females exposed to 0.3, 3, or 30 µg/L atrazine during embryogenesis were identified, respectively. There was a high level of overlap between the biological processes and molecular pathways in which the altered genes were associated. Moreover, a subset of genes was down regulated throughout the serotonergic pathway. These results provide support of the developmental origins of neurological alterations observed in adult female zebrafish exposed to atrazine during embryogenesis.

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Repeated exposure to the herbicide atrazine alters locomotor activity and the nigrostriatal dopaminergic system of the albino rat

Cited by 56 publications

References 45 publications

Developmental Exposure to Atrazine Impairs Spatial Memory and Downregulates the Hippocampal D1 Dopamine Receptor and cAMP-Dependent Signaling Pathway in Rats

Developmental Exposure to Atrazine Impairs Spatial Memory and Downregulates the Hippocampal D1 Dopamine Receptor and cAMP-Dependent Signaling Pathway in Rats

Isoflavones Induce BEX2-Dependent Autophagy to Prevent ATR-Induced Neurotoxicity in SH-SY5Y Cells

Developmental origins of neurotransmitter and transcriptome alterations in adult female zebrafish exposed to atrazine during embryogenesis

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