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

Xingwang Ding; Ya Wen; Xuan Ma; Yuepei Zhang; Yuting Cheng; Zhaofeng Liu; Weiyue Hu; Yankai Xia

doi:10.1016/j.ese.2022.100224

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

Environ Sci Ecotechnol. 2022 Nov 14:13:100224. doi: 10.1016/j.ese.2022.100224. eCollection 2023 Jan.

Authors

Xingwang Ding^{1

2}, Ya Wen^{1

3}, Xuan Ma^{1

2}, Yuepei Zhang^{1

2}, Yuting Cheng^{1

2}, Zhaofeng Liu^{1

2}, Weiyue Hu^{1

4}, Yankai Xia^{1

2}

Affiliations

¹ State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
² Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
³ Department of Chronic Non-Communicable Disease Control, Wuxi Liangxi District Center for Disease Control and Prevention, Wuxi, 214011, China.
⁴ Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

Abstract

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.

Keywords: Anxiety-like behaviors; Prenatal exposure; Pyridaben; Pyridoxal 5′-phosphate.