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Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring

Pyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here,...

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Autores principales: Ding, Xingwang, Wen, Ya, Ma, Xuan, Zhang, Yuepei, Cheng, Yuting, Liu, Zhaofeng, Hu, Weiyue, Xia, Yankai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691908/
https://www.ncbi.nlm.nih.gov/pubmed/36437888
http://dx.doi.org/10.1016/j.ese.2022.100224
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author Ding, Xingwang
Wen, Ya
Ma, Xuan
Zhang, Yuepei
Cheng, Yuting
Liu, Zhaofeng
Hu, Weiyue
Xia, Yankai
author_facet Ding, Xingwang
Wen, Ya
Ma, Xuan
Zhang, Yuepei
Cheng, Yuting
Liu, Zhaofeng
Hu, Weiyue
Xia, Yankai
author_sort Ding, Xingwang
collection PubMed
description Pyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here, we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg(−1) day(−1) via gavage and observed anxiety-like behaviors in PY offspring aged five weeks. We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism. Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected, and the pyridoxal 5′-phosphate (PLP) concentration and the active form of vitamin B6 was significantly reduced. Moreover, the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated. Meanwhile, there was a decreasing trend in the concentration of GABA in the hippocampal DG region. Next, we supplemented PLP at a dose of 20 mg kg(−1) day(−1) to the PY offspring via intraperitoneal injection at three weeks. We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors. This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism, reduce the concentration of PLP, down-regulate the expression levels of Pdxk and Gad1, inhibit the production of GABA, and ultimately lead to anxiety-like behaviors in offspring.
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spelling pubmed-96919082022-11-26 Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring Ding, Xingwang Wen, Ya Ma, Xuan Zhang, Yuepei Cheng, Yuting Liu, Zhaofeng Hu, Weiyue Xia, Yankai Environ Sci Ecotechnol Original Research Pyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here, we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg(−1) day(−1) via gavage and observed anxiety-like behaviors in PY offspring aged five weeks. We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism. Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected, and the pyridoxal 5′-phosphate (PLP) concentration and the active form of vitamin B6 was significantly reduced. Moreover, the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated. Meanwhile, there was a decreasing trend in the concentration of GABA in the hippocampal DG region. Next, we supplemented PLP at a dose of 20 mg kg(−1) day(−1) to the PY offspring via intraperitoneal injection at three weeks. We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors. This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism, reduce the concentration of PLP, down-regulate the expression levels of Pdxk and Gad1, inhibit the production of GABA, and ultimately lead to anxiety-like behaviors in offspring. Elsevier 2022-11-14 /pmc/articles/PMC9691908/ /pubmed/36437888 http://dx.doi.org/10.1016/j.ese.2022.100224 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Ding, Xingwang
Wen, Ya
Ma, Xuan
Zhang, Yuepei
Cheng, Yuting
Liu, Zhaofeng
Hu, Weiyue
Xia, Yankai
Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_full Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_fullStr Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_full_unstemmed Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_short Pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
title_sort pyridoxal 5′-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691908/
https://www.ncbi.nlm.nih.gov/pubmed/36437888
http://dx.doi.org/10.1016/j.ese.2022.100224
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