PUBLICATION
Early-life perfluorooctanoic acid exposure disrupts the function of dopamine transporter protein with glycosylation changes implicating the links between decreased dopamine levels and disruptive behaviors in larval zebrafish
- Authors
- Du, Y., Li, Q., Zhou, G., Cai, Z., Man, Q., Wang, W.C.
- ID
- ZDB-PUB-240129-5
- Date
- 2024
- Source
- The Science of the total environment 917: 170408 (Journal)
- Registered Authors
- Keywords
- Anxiety, Depression, Dopamine, ER stress, PFOA, Zebrafish
- MeSH Terms
-
- Animals
- Caprylates*
- Child
- Dopamine
- Dopamine Plasma Membrane Transport Proteins/genetics
- Dopamine Plasma Membrane Transport Proteins/metabolism
- Dopamine Plasma Membrane Transport Proteins/pharmacology
- Female
- Fluorocarbons*
- Glycosylation
- Humans
- Larva
- Pregnancy
- Problem Behavior*
- Zebrafish*
- PubMed
- 38281643 Full text @ Sci. Total Environ.
Citation
Du, Y., Li, Q., Zhou, G., Cai, Z., Man, Q., Wang, W.C. (2024) Early-life perfluorooctanoic acid exposure disrupts the function of dopamine transporter protein with glycosylation changes implicating the links between decreased dopamine levels and disruptive behaviors in larval zebrafish. The Science of the total environment. 917:170408.
Abstract
Exposure to perfluorooctanoic acid (PFOA) during early embryonic development is associated with the increased risk of developmental neurotoxicity and neurobehavioral disorders in children. In our previous study, we demonstrated that exposure to PFOA affected locomotor activity and disrupted dopamine-related gene expression in zebrafish larvae. Consequently, we continue to study the dopaminergic system with a focus on dopamine levels and dopamine's effect on behaviors in relation to PFOA exposure. In the present study, we found a decrease in dopamine levels in larval zebrafish. We studied the dopamine transporter (DAT) protein, which is responsible for regulating dopamine levels through the reuptake of dopamine in neuronal cells. We demonstrated that exposure to PFOA disrupted the glycosylation process of DAT, inhibited its uptake function, and induced endoplasmic reticulum (ER) stress in dopaminergic cells. Besides, we conducted a light-dark preference test on larval zebrafish and observed anxiety/depressive-like behavioral changes following exposure to PFOA. Dopamine is one of the most prominent neurotransmitters that significantly influences human behavior, with low dopamine levels being associated with impairments such as anxiety and depression. The anxiety-like response in zebrafish larvae exposure to PFOA implies the link with the reduced dopamine levels. Taken together, we can deduce that glycosylation changes in DAT lead to dysfunction of DAT to regulate dopamine levels, which in turn alters behavior in larval zebrafish. Therefore, alternation in dopamine levels may play a pivotal role in the development of anxiety/depressive-like behavioral changes induced by PFOA.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping