Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma
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...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/2/655 |
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| author | Tin-Tin Win-Shwe Rie Yanagisawa Thet-Thet Lwin Fumitaka Kawakami Eiko Koike Hirohisa Takano |
| author_facet | Tin-Tin Win-Shwe Rie Yanagisawa Thet-Thet Lwin Fumitaka Kawakami Eiko Koike Hirohisa Takano |
| author_sort | Tin-Tin Win-Shwe |
| collection | DOAJ |
| description | 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 <i>(Iba)-1</i> immunoreactivity, respectively. Impaired discrimination ability was observed in TBEP-H-exposed mice with or without allergen. The mRNA expression levels of <i>N</i>-methyl-<i>D</i> aspartate receptor subunits <i>Nr1</i> and <i>Nr2b</i>, inflammatory molecular markers tumor necrosis factor-α oxidative stress marker heme oxygenase 1, microglia marker <i>Iba1,</i> 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. |
| first_indexed | 2024-03-10T01:20:19Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:20:19Z |
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| spelling | doaj.art-b493f03c65024d1bafd54121fcd8ca652023-11-23T14:02:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-0123265510.3390/ijms23020655Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic AsthmaTin-Tin Win-Shwe0Rie Yanagisawa1Thet-Thet Lwin2Fumitaka Kawakami3Eiko Koike4Hirohisa Takano5Health and Environmental Risk Division, National Institute for Environmental Studies, Tsukuba 305-8506, JapanHealth and Environmental Risk Division, National Institute for Environmental Studies, Tsukuba 305-8506, JapanSchool of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, JapanSchool of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, JapanHealth and Environmental Risk Division, National Institute for Environmental Studies, Tsukuba 305-8506, JapanGraduate School of Global Environmental Studies, Kyoto University, Kyoto 615-8530, JapanTris (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 <i>(Iba)-1</i> immunoreactivity, respectively. Impaired discrimination ability was observed in TBEP-H-exposed mice with or without allergen. The mRNA expression levels of <i>N</i>-methyl-<i>D</i> aspartate receptor subunits <i>Nr1</i> and <i>Nr2b</i>, inflammatory molecular markers tumor necrosis factor-α oxidative stress marker heme oxygenase 1, microglia marker <i>Iba1,</i> 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.https://www.mdpi.com/1422-0067/23/2/655tris (2-butoxyethyl) phosphate (TBEP)novel object recognition testinflammatory biomarkershippocampusallergic asthmatic mouse |
| spellingShingle | Tin-Tin Win-Shwe Rie Yanagisawa Thet-Thet Lwin Fumitaka Kawakami Eiko Koike Hirohisa Takano Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma International Journal of Molecular Sciences tris (2-butoxyethyl) phosphate (TBEP) novel object recognition test inflammatory biomarkers hippocampus allergic asthmatic mouse |
| title | Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma |
| title_full | Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma |
| title_fullStr | Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma |
| title_full_unstemmed | Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma |
| title_short | Dietary Exposure to Flame Retardant Tris (2-Butoxyethyl) Phosphate Altered Neurobehavior and Neuroinflammatory Responses in a Mouse Model of Allergic Asthma |
| title_sort | dietary exposure to flame retardant tris 2 butoxyethyl phosphate altered neurobehavior and neuroinflammatory responses in a mouse model of allergic asthma |
| topic | tris (2-butoxyethyl) phosphate (TBEP) novel object recognition test inflammatory biomarkers hippocampus allergic asthmatic mouse |
| url | https://www.mdpi.com/1422-0067/23/2/655 |
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