PUBLICATION
Changes in aggression and locomotor behaviors in response to zinc is accompanied by brain cell heterogeneity and metabolic and circadian dysregulation of the brain-liver axis
- Authors
- Yu, F., Luo, H.R., Cui, X.F., Wu, Y.J., Li, J.L., Feng, W.R., Tang, Y.K., Su, S.Y., Xiao, J., Hou, Z.S., Xu, P.
- ID
- ZDB-PUB-221122-1
- Date
- 2022
- Source
- Ecotoxicology and environmental safety 248: 114303 (Journal)
- Registered Authors
- Keywords
- Animal model, Behavior, Environmental toxicology, Physiology, Zebrafish, Zinc
- MeSH Terms
-
- Liver
- Chronobiology Disorders*
- Zinc/toxicity
- Aggression
- Amyloid beta-Peptides
- Brain
- Animals
- Zebrafish*
- PubMed
- 36403304 Full text @ Ecotoxicol. Environ. Saf.
Citation
Yu, F., Luo, H.R., Cui, X.F., Wu, Y.J., Li, J.L., Feng, W.R., Tang, Y.K., Su, S.Y., Xiao, J., Hou, Z.S., Xu, P. (2022) Changes in aggression and locomotor behaviors in response to zinc is accompanied by brain cell heterogeneity and metabolic and circadian dysregulation of the brain-liver axis. Ecotoxicology and environmental safety. 248:114303.
Abstract
Zinc is an essential nutrient for life, but over-accumulation can result in toxicity. Anthropogenic activities can increase zinc concentrations in aquatic environments (e.g., to ∼0.46-1.00 mg/L), which are above the safe level of 0.1 mg/L. We investigated the behavior and physiology of zebrafish (Danio rerio) in response to environment-related exposure to zinc chloride at 0.0 (Ctrl), 1.0 (ZnCl2-low) and 1.5 (ZnCl2-high) mg/L for 6 weeks (the zinc conversion ratio of zinc chloride is ∼0.48 and the nominal (measured) values were: Ctrl, 0 (∼0.01); ZnCl2-low, 0.48 (∼0.51); ZnCl2-high, 0.72 (∼0.69) mg/L). Low-zinc exposure resulted in significantly increased locomotion and fast moving behaviors, while high-zinc exposure resulted in significantly increased aggression and freezing frequency. Single cell RNA-seq of neurons, astrocytes, and oligodendrocytes of the brain revealed expression of genes related to ion transport, neuron generation, and immunomodulation that were heterogeneously regulated by zinc exposure. Astrocyte-induced central nervous system inflammation potentially integrated neurotoxicity and behavior. Integrated analyses of brain and hepatic transcriptional signatures showed that genes (and pathways) dysregulated by zinc were associated with sensory functions, circadian rhythm, glucose and lipid metabolism, and amyloid β-protein clearance. Our results showed that environment-related zinc contamination can be heterogeneously toxic to brain cells and can disturb coordination of brain-liver physiology. This may disrupt neurobehavior and cause a neurodegeneration-like syndrome in adult zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping