TY - JOUR
T1 - Mechanism of action and neurotoxic effects of chronic exposure to bisphenol F in adult zebrafish
AU - Kim, Seong Soon
AU - Kim, Jiwon L.
AU - Hwang, Kyu Seok
AU - Park, Hae Chul
AU - Bae, Myung Ae
AU - Kim, Ki Tae
AU - Cho, Sung Hee
N1 - Funding Information:
This work was supported by the Korea Environment Industry & Technology Institute (KEITI) through the Technology Development Project for Safety Management of Household Chemical Products , funded by the Korea Ministry of Environment ( MOE ) ( 2020002960007 , NTIS-1485017544 ), and by project of Korea Research Institute of Chemical Technology ( KK2252-10 & SI2231-40 ), Republic of Korea. This work was also partially supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grants No. NRF-2020R1A6A1A03042742 ).
Publisher Copyright:
© 2022
PY - 2022/12/10
Y1 - 2022/12/10
N2 - Although bisphenol F (BPF), the main replacement for bisphenol A, has been commonly used in polycarbonate production, its neurotoxicity and the underlying mechanisms remain poorly understood. To address this knowledge gap, this study aimed to assess the neurotoxicity caused by chronic exposure to BPF and to identify its underlying mechanisms. We exposed adult zebrafish chronically to BPF at environmentally relevant concentrations (0.001, 0.01, and 0.1 mg/L) for 4 weeks. The results revealed that with BPF crossing the blood–brain barrier and bioaccumulating in brain tissues, chronic exposure to BPF resulted in anxiety-like behaviors and disruptions in learning and memory function in adult zebrafish. Furthermore, BPF toxicity in the zebrafish brain involved the dysregulation of metabolic pathways for choline and kynurenine in neurotransmitter systems and for 17β-estradiol, cortisol, pregnenolone-sulfate, and Dehydroepiandrosterone (DHEA)-sulfate in neurosteroid systems. RNA-seq analysis revealed that BPF exposure affected metabolic pathways, calcium signaling pathways, neuroactive ligand–receptor interactions, tight junctions, gap junctions, and the gonadotropin-releasing hormone signaling pathway. Our results indicate that chronic exposure to BPF alters the neurochemical profile of the brain and causes neurobehavioral effects, such as anxiety and cognitive decline. Overall, the multimodal approach, including behavioral and neurochemical profiling technologies, has great potential for the comprehensive assessment of potential risks posed by environmental pollutants to human and ecosystem health.
AB - Although bisphenol F (BPF), the main replacement for bisphenol A, has been commonly used in polycarbonate production, its neurotoxicity and the underlying mechanisms remain poorly understood. To address this knowledge gap, this study aimed to assess the neurotoxicity caused by chronic exposure to BPF and to identify its underlying mechanisms. We exposed adult zebrafish chronically to BPF at environmentally relevant concentrations (0.001, 0.01, and 0.1 mg/L) for 4 weeks. The results revealed that with BPF crossing the blood–brain barrier and bioaccumulating in brain tissues, chronic exposure to BPF resulted in anxiety-like behaviors and disruptions in learning and memory function in adult zebrafish. Furthermore, BPF toxicity in the zebrafish brain involved the dysregulation of metabolic pathways for choline and kynurenine in neurotransmitter systems and for 17β-estradiol, cortisol, pregnenolone-sulfate, and Dehydroepiandrosterone (DHEA)-sulfate in neurosteroid systems. RNA-seq analysis revealed that BPF exposure affected metabolic pathways, calcium signaling pathways, neuroactive ligand–receptor interactions, tight junctions, gap junctions, and the gonadotropin-releasing hormone signaling pathway. Our results indicate that chronic exposure to BPF alters the neurochemical profile of the brain and causes neurobehavioral effects, such as anxiety and cognitive decline. Overall, the multimodal approach, including behavioral and neurochemical profiling technologies, has great potential for the comprehensive assessment of potential risks posed by environmental pollutants to human and ecosystem health.
KW - Bisphenol F
KW - Neurobehavior
KW - Neurochemicals
KW - Neurotoxicity
KW - Transcriptomics
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85137112634&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2022.158258
DO - 10.1016/j.scitotenv.2022.158258
M3 - Article
C2 - 36030852
AN - SCOPUS:85137112634
SN - 0048-9697
VL - 851
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 158258
ER -