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
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
复制标题
锌对攻击性和运动行为的改变伴随着脑细胞异质性以及脑肝轴的代谢和昼夜节律失调
DOI：
10.1016/j.ecoenv.2022.114303
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发表时间：
2022
影响因子：
6.8
通讯作者：
Pao Xu
中科院分区：
文献类型：
--
作者：
Fan Yu;Hong-Rui Luo;Xue-Fan Cui;Yi-Jie Wu;Jian-Lin Li;Wen-Rong Feng;Yong-Kai Tang;Sheng-Yan Su;Jun Xiao;Zhi-Shuai Hou;Pao Xu
锌是生命所必需的营养物质，但过量积累会导致中毒。人为活动可使水环境中的锌浓度升高(∼为0.46-1.00 mg/L)，高于0.1m g/L的安全水平。研究了斑马鱼(Danio Rerio)在与环境有关的氯化锌浓度为0.01m g/L、1.0m g/L和1.5m g/L暴露6周后的行为和生理变化(氯化锌的锌转化率为0.48，标称值为：Ctrl，0(∼0.01)；低锌，0.48(∼0.51)；高锌，0.72(∼0.69)mg/L)。低锌暴露导致大鼠的运动和快速移动行为显著增加，而高锌暴露导致攻击和冰冻频率显著增加。脑神经元、星形胶质细胞和少突胶质细胞的单细胞RNA-SEQ显示，与离子转运、神经元生成和免疫调节相关的基因表达受锌暴露的异质性调节。星形胶质细胞诱导的中枢神经系统炎症可能整合了神经毒性和行为。对大脑和肝脏转录特征的综合分析表明，锌调控失调的基因(和途径)与感觉功能、昼夜节律、葡萄糖和脂肪代谢以及淀粉样蛋白β-蛋白质清除有关。我们的结果表明，与环境相关的锌污染可以对脑细胞产生异质性毒性，并可以扰乱脑-肝生理的协调。这可能会扰乱成年斑马鱼的神经行为，并导致类似神经退化的综合症。
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.