Abstract
Tris (2-butoxyethyl) phosphate (TBEP) is an organophosphate flame retardant and used as a plasticizer in various household products such as plastics, floor polish, varnish, textiles, furniture, and electronic equipment. However, little is known about the effects of TBEP on the brain and behavior. We aimed to examine the effects of dietary exposure of TBEP on memory functions, their-related genes, and inflammatory molecular markers in the brain of allergic asthmatic mouse models. C3H/HeJSlc male mice were given diet containing TBEP (0.02 (TBEP-L), 0.2 (TBEP-M), or 2 (TBEP-H) μg/kg/day) and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. A novel object recognition test was conducted in each mouse at 11 weeks old. The hippocampi were collected to detect neurological, glia, and immunological molecular markers using the real-time RT-PCR method and immunohistochemical analyses. Mast cells and microglia were examined by toluidine blue staining and ionized calcium-binding adapter molecule (Iba)-1 immunoreactivity, respectively. Impaired discrimination ability was observed in TBEP-H-exposed mice with or without allergen. The mRNA expression levels of N-methyl-D aspartate receptor subunits Nr1 and Nr2b, inflammatory molecular markers tumor necrosis factor-α oxidative stress marker heme oxygenase 1, microglia marker Iba1, and astrocyte marker glial fibrillary acidic protein were significantly increased in TBEP-H-exposed mice with or without allergen. Microglia and mast cells activation were remarkable in TBEP-H-exposed allergic asthmatic mice. Our results indicate that chronic exposure to TBEP with or without allergen impaired object recognition ability accompanied with alteration of molecular expression of neuronal and glial markers and inflammatory markers in the hippocampus of mice. Neuron-glia-mast cells interaction may play a role in TBEP-induced neurobehavioral toxicity.
Highlights
To detect the in the hippocampus, wehave havealso alsoinvesinvesTo detect the Tris (2-butoxyethyl) phosphate (TBEP)-induced inflammation in the hippocampus, we have investigated the inflammatory molecular markers such as interleukin (Il)-1β, tumor necrosis tigated the inflammatory molecular markers such as interleukin (Il)-1β, tumor necrosis tigated the inflammatory molecular markers such as interleukin (Il)-1β, tumor necrosis factor αα and heme oxygenase (Ho)-1 and ionized calcium-binding adapter molecule factor (Tnf) and factor (Tnf) α and heme heme oxygenase oxygenase (Ho)-1 (Ho)-1 and and ionized ionized calcium-binding calcium-binding adapter adapter molecule molecule (Iba)1 in the hippocampus hippocampusof ofmice micewith withororwithout without
The major findings of the present study were that oral exposure to TBEP (1) impairs novel object recognition ability accompanied with abnormal activation of memory functionrelated gene Nmda receptor subunits, (2) induces upregulation of proinflammatory cytokine
We found that the expression levels of Nr1 and Nr2b mRNAs were significantly increased in TBEP-H and OVA + TBEP-H exposed group compared with the vehicle-alone group (Figure 3)
Summary
Tris (2-butoxyethyl) phosphate (TBEP) is one of the organophosphate flame retardants (OPFRs). Flame retardants (FRs) are extensively used in construction materials, textiles, and electrical appliances around the world. Some of FRs, such as polybrominated diphenyl ethers and hexabromocyclododecane, have been banned for toxicity, and OPFRs are used to replace toxic FRs. it is necessary to examine the biological effect of exposure to TBEP, which is a commonly used OPER. Recent studies have shown that OPFRs have neurotoxic effects and potential carcinogenic effects in different animal studies [1–4]. OPFRs are released into the environment from consumer products, and humans can be exposed
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