PUBLICATION
Long-Term Neurotoxic Effects and Alzheimer's Disease Risk of Early EHDPP Exposure in Zebrafish: Insights from Molecular Mechanisms to Adult Pathology
- Authors
- Yan, J., Fang, L., Ni, A., Xi, M., Li, J., Zhou, X., Qian, Q., Wang, Z.J., Wang, X., Wang, H.
- ID
- ZDB-PUB-241018-15
- Date
- 2024
- Source
- Environmental science & technology 58(43): 19152-19164 (Journal)
- Registered Authors
- Keywords
- 2-ethylhexyl diphenyl phosphate (EHDPP), AD-like symptom, disordered Ca2+ homeostasis, long-term neurotoxicity, zebrafish
- MeSH Terms
-
- Zebrafish*
- Animals
- Alzheimer Disease*
- PubMed
- 39417326 Full text @ Env. Sci. Tech.
Citation
Yan, J., Fang, L., Ni, A., Xi, M., Li, J., Zhou, X., Qian, Q., Wang, Z.J., Wang, X., Wang, H. (2024) Long-Term Neurotoxic Effects and Alzheimer's Disease Risk of Early EHDPP Exposure in Zebrafish: Insights from Molecular Mechanisms to Adult Pathology. Environmental science & technology. 58(43):19152-19164.
Abstract
2-Ethylhexyl diphenyl phosphate (EHDPP), ubiquitously monitored in environmental media, is highly bioaccumulative and may pose long-term risks, even after short-term exposure. In this investigation, larval zebrafish were exposed to 0.05, 0.5, and 5.0 μg/L EHDPP from 4 to 120 h postfertilization (hpf) to examine the long-term neurotoxicity effects of early exposure. Exposure to 5.0 μg/L EHDPP yielded hyperactive locomotor behavior, which was characterized by increased swimming speed, larger turning angles, and heightened sensitivity to light-dark stimulation. The predicted targets of EHDPP (top 100 potential macromolecules) were primarily associated with brain diseases like Alzheimer's disease (AD). Comparisons of differentially expressed genes (DEGs) from AD patients (GSE48350) and RNA-seq data from EHDPP-exposed zebrafish confirmed consistently abnormal regulatory pathways. EHDPP's interaction with M1 and M5 muscarinic acetylcholine receptors likely disrupted calcium homeostasis, leading to mitochondrial dysfunction and neurotransmitter imbalance as well as abnormal locomotor behavior. Especially, 5.0 μg/L EHDPP exposure during early development (4-120 hpf) triggered early- and midstage AD-like symptoms in adulthood (180 dpf), characterized by cognitive confusion, aggression, blood-brain barrier disruption, and mitochondrial damage in brains. These findings provide deep insights into the long-term neurotoxicity effects and Alzheimer's disease risks of early EHDPP exposure at extremely low dosages.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping