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

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

PMC · DOI: 10.1371/journal.pone.0140281 · PLoS ONE · 2015-10-12

## TL;DR

A new chemical pollutant harms the brains of adult rats, causing memory problems and depression-like symptoms.

## Contribution

This study is the first to show that TDBP-TAZTO causes neurotoxicity in adult rats, linking it to cognitive and behavioral impairments.

## Key findings

- TDBP-TAZTO exposure leads to cognitive impairment and depression-like behaviors in adult rats.
- The chemical causes hippocampal neuron damage and disrupts neurogenesis-related proteins.
- TDBP-TAZTO activates the HPA axis and increases oxidative stress and inflammation in the brain.

## 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.

## Linked entities

- **Chemicals:** Tris-(2,3-dibromopropyl) isocyanurate (PubChem CID 103634)
- **Diseases:** depression (MONDO:0002050)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Syp (synaptophysin) [NCBI Gene 20977] {aka A230093K24Rik, Syn, p38}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], SYP (synaptophysin) [NCBI Gene 6855] {aka MRX96, MRXSYP, XLID96}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Gfap (glial fibrillary acidic protein) [NCBI Gene 24387], Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Cort (cortistatin) [NCBI Gene 25305], BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, CORT (cortistatin) [NCBI Gene 1325] {aka CST-14, CST-17, CST-29, SST2}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}
- **Diseases:** inflammation (MESH:D007249), weight gain (MESH:D015430), adrenal hyperplasia (MESH:D000312), HPA axis (MESH:D007029), CNS diseases (MESH:D002493), hypertrophy (MESH:D006984), neurodegenerative and depression-like disorders (MESH:D019636), endocrine toxic effects (MESH:D004700), hyperplasia (MESH:D006965), Cognition (MESH:D003072), axis (MESH:C566610), neurotoxic (MESH:D020258), motor deficits (MESH:D009461), hypertrophy of the zona fasciculata (MESH:D006562), Depression (MESH:D003866), atrophy (MESH:D001284), fire-related injury (MESH:D014947), impaired learning performance (MESH:D007859), hippocampal neurons damage (MESH:D009410), liver and lung toxicity (MESH:D056486), Neuroinflammation (MESH:D000090862), toxicity (MESH:D064420), Mortality (MESH:D003643),  (MESH:D008569)
- **Chemicals:** phosphate (MESH:D010710), lipid (MESH:D008055), polybrominated diphenylethers (MESH:D055768), hematoxylin (MESH:D006416), GSH (MESH:D005978), heparin (MESH:D006493), CORT (MESH:D003345), paraffin (MESH:D010232), 3,3-diaminobenzidine (MESH:D015100), Tris-(2,3-Dibromopropyl) Isocyanurate (MESH:C541743), BCA (-), H2O2 (MESH:D006861), water (MESH:D014867), chloral hydrate (MESH:D002697), HE (MESH:D006371), citrate (MESH:D019343), fatty acids (MESH:D005227), tetrabromobisphenol-A (MESH:C020806), alcohol (MESH:D000438), methanol (MESH:D000432), corn oil (MESH:D003314),  (MESH:D016708),  (MESH:D009498),  (MESH:D016207),  (MESH:D014227),  (MESH:D019208),  (MESH:D000324),  (MESH:D015415),  (MESH:D004785)
- **Species:** Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Mus musculus (house mouse, species) [taxon 10090], Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC4601767/full.md

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4601767/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC4601767/full.md

---
Source: https://tomesphere.com/paper/PMC4601767