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The environmental pollutant BDE-209 regulates NO/cGMP signaling through activation of NMDA receptors in neurons

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Abstract

The common flame retardant decabrominated diphenyl ether (BDE-209) is a persistent organic pollutant. Epidemiological studies have revealed that prenatal or postnatal exposure to BDE-209 can result in delayed cognitive development, and BDE-209 has been shown to be toxic to cultured neurons with maturation interference effects. However, its neurotoxic mechanism remains unclear. Nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling plays an important role in regulating neuronal maturation. We examined the influence of BDE-209 (100, 200, and 400 nM) on NO production and cGMP levels signaling in rodent neurons in vitro, with or without pretreatment N-methyl-D-aspartate (NMDA) receptor antagonism. We found that nanomolar concentrations of BDE-209 affected levels of the second messengers NO and cGMP, and that these effects could be blocked by NMDA receptor antagonism. Moreover, BDE-209 activation of NMDA receptors inhibited the expression of phosphodiesterases (PDEs), which modulate intracellular cGMP levels, and increased the Bcl-2/Bax ratio, favoring apoptosis induction. Our studies implicate the NMDA-NO/cGMP pathway in the pathogenic mechanism through which BDE-209 induces neurotoxicity.

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Funding

This work was supported by the Chinese National Nature Science Grants (Youth Project 81402652 and General Project 81571518).

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Authors and Affiliations

  1. Department of Fetal Medicine and Prenatal Diagnosis, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China

    Jingsi Chen

  2. Obstetrics & Gynecology Institute of Guangzhou, Guangzhou, 510150, China

    Jingsi Chen, Xiuying Li, Xiaomei Li & Dunjin Chen

  3. Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, People’s Republic of China, Guangzhou, 510150, China

    Jingsi Chen & Dunjin Chen

  4. Key Laboratories for Major Obstetric Diseases of Guangdong Province, Guangzhou, 510150, China

    Jingsi Chen & Dunjin Chen

  5. No.63, Duobao Road, Guangzhou, 510150, China

    Dunjin Chen

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  1. Jingsi Chen
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  2. Xiuying Li
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  3. Xiaomei Li
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  4. Dunjin Chen
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Correspondence to Dunjin Chen.

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Chen, J., Li, X., Li, X. et al. The environmental pollutant BDE-209 regulates NO/cGMP signaling through activation of NMDA receptors in neurons. Environ Sci Pollut Res 25, 3397–3407 (2018). https://doi.org/10.1007/s11356-017-0651-5

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  • DOI: https://doi.org/10.1007/s11356-017-0651-5

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