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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

文献类型： 外文期刊

作者： Yu, Fan 1 ; Luo, Hong-Rui 2 ; Cui, Xue-Fan 2 ; Wu, Yi-Jie 3 ; Li, Jian-Lin 1 ; Feng, Wen-Rong 1 ; Tang, Yong-Kai 1 ; Su, Sheng-Yan 1 ; Xiao, Jun 3 ; Hou, Zhi-Shuai 4 ; Xu, Pao 1 ;

作者机构： 1.Chinese Acad Fishery Sci, Freshwater Fisheries Res Ctr, Key Lab Freshwater Fisheries & Germplasm Resources, Minist Agr & Rural Affairs, Wuxi 214081, Peoples R China

2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China

3.Key Lab Comprehens Dev & Utilizat Aquat Germplasm, Nanning 530021, Peoples R China

4.Ocean Univ China, Key Lab Mariculture, Minist Educ KLMME, Qingdao 266003, Peoples R China

关键词： Environmental toxicology; Animal model; Zebrafish; Zinc; Behavior; Physiology

期刊名称：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY （ 影响因子：6.8； 五年影响因子：6.9 ）

ISSN： 0147-6513

年卷期： 2022 年 248 卷

页码：

收录情况： SCI

摘要： 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 beta-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.

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