Tris-(2,3-Dibromopropyl) Isocyanurate, a New Emerging Pollutant, Impairs Cognition and Provokes Depression-Like Behaviors in Adult Rats

Liang Ye; Zhengping Hu; Hui Wang; Haibo Zhu; Zhaoju Dong; Wanglin Jiang; Huijuan Zhao; Ning Li; Wei Mi; Wenyan Wang; Xihou Hu

doi:10.1371/journal.pone.0140281

Tris-(2,3-Dibromopropyl) Isocyanurate, a New Emerging Pollutant, Impairs Cognition and Provokes Depression-Like Behaviors in Adult Rats

PLoS One. 2015 Oct 12;10(10):e0140281. doi: 10.1371/journal.pone.0140281. eCollection 2015.

Authors

Liang Ye¹, Zhengping Hu², Hui Wang³, Haibo Zhu¹, Zhaoju Dong⁴, Wanglin Jiang⁵, Huijuan Zhao⁴, Ning Li⁴, Wei Mi⁴, Wenyan Wang³, Xihou Hu⁴

Affiliations

¹ School of Public Health and Management, Binzhou Medical University, Yantai, Shandong, PR China; Institute of Toxicology, Binzhou Medical University, Yantai, Shandong, PR China.
² Medicine & Pharmacy Research Center, Binzhou Medical University, Yantai, Shandong, PR China.
³ School of Pharmacy, Yantai University, Yantai, Shandong, PR China.
⁴ School of Public Health and Management, Binzhou Medical University, Yantai, Shandong, PR China.
⁵ School of Pharmacy, Binzhou Medical University, Yantai, Shandong, PR China.

Abstract

Tris-(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), an emerging brominated flame retardant, possesses the characteristics of candidate persistent organic pollutants and has displayed toxicity to fish and rodents. TDBP-TAZTO can pass through the blood brain barrier and accumulate in brain. However, the neurotoxicity of TDBP-TAZTO has not yet studied in rodents. We hypothesize that TDBP-TAZTO could induce the neurotoxicity in rat hippocampal neurons. The male adult rats were exposed to TDBP-TAZTO of 5 and 50 mg/kg by gavage, daily for 6 months. TDBP-TAZTO resulted in cognitive impairment and depression-like behaviors, which may be related with TDBP-TAZTO-induced hypothalamic-pituitary-adrenal axis hyperactivation, upregulation of inflammatory and oxidative stress markers, overexpression of pro-apoptotic proteins, downexpression of neurogenesis-related proteins in hippocampus, and hippocampal neurons damage in DG, CA1 and CA3 areas. Our findings suggested that TDBP-TAZTO induces significant hippocampal neurotoxicity, which provokes cognitive impairment and depression-like behaviors in adult rats. Therefore, this research will contribute to evaluate the neurotoxic effects of TDBP-TAZTO in human.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenocorticotropic Hormone / blood
Animals
Behavior, Animal / drug effects*
Biomarkers / metabolism
Brain-Derived Neurotrophic Factor / metabolism
Cognition / drug effects*
Corticosterone / blood
Cytokines / metabolism
Depression / chemically induced*
Depression / metabolism
Depression / pathology
Depression / physiopathology*
Environmental Pollutants / toxicity*
Gene Expression Regulation / drug effects
Hippocampus / drug effects
Hippocampus / metabolism
Hippocampus / pathology
Hippocampus / physiopathology
Hypothalamo-Hypophyseal System / drug effects
Male
Memory / drug effects
Motor Activity / drug effects
Neurogenesis / drug effects
Neurons / drug effects
Neurons / pathology
Neurotoxins / toxicity*
Oxidative Stress / drug effects
Rats
Rats, Sprague-Dawley
Synaptophysin / metabolism
Triazines / toxicity*

Substances

Biomarkers
Brain-Derived Neurotrophic Factor
Cytokines
Environmental Pollutants
Neurotoxins
Synaptophysin
Triazines
tris(2,3-dibromopropyl)isocyanurate
Adrenocorticotropic Hormone
Corticosterone

Grants and funding

This work was supported by the Natural Science Foundation of Shandong Province, China (No. ZR2014HM091), the Scientific Research Foundation of Binzhou Medical College, Shandong Province, China (No. BY2013KYQD21) and the Outstanding Young Scientist Research Award Foundation of Shandong Province (No. BS2014YY008).