Acrylamide acute neurotoxicity in adult zebrafish.

Acrylamide acute neurotoxicity in adult zebrafish.
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DOI:
10.1038/s41598-018-26343-2
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发表时间:
2018-05-21
期刊:
影响因子:
4.6
通讯作者:
Raldúa D
Raldúa D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Faria M;Ziv T;Gómez-Canela C;Ben-Lulu S;Prats E;Novoa-Luna KA;Admon A;Piña B;Tauler R;Gómez-Oliván LM;Raldúa D

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急性接触丙烯酰胺(ACR),一种2型烯烃,可导致人类和实验动物的共济失调、骨骼肌无力和四肢麻木。在目前的手稿中,ACR急性神经毒性的特点是在成年斑马鱼,脊椎动物模型越来越多地用于人类神经药理学和毒理学研究。在行为水平上,ACR处理的动物表现出与焦虑行为共病的“抑郁样”表型。在转录水平上,ACR诱导再生相关基因的下调和少突胶质细胞和反应性星形胶质细胞标记物的上调,也改变了参与突触前囊泡循环的基因的表达。ACR还诱导斑马鱼脑蛋白质组的显着变化,并与特定蛋白质的选定半胱氨酸残基形成加合物,其中一些是突触前功能所必需的。最后,代谢组学分析显示,在暴露的鱼的大脑中,与抑郁症和焦虑症共病一致的单胺神经递质的消耗。
Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR acute neurotoxicity has been characterized in adult zebrafish, a vertebrate model increasingly used in human neuropharmacology and toxicology research. At behavioral level, ACR-treated animals exhibited “depression-like” phenotype comorbid with anxiety behavior. At transcriptional level, ACR induced down-regulation of regeneration-associated genes and up-regulation of oligodendrocytes and reactive astrocytes markers, altering also the expression of genes involved in the presynaptic vesicle cycling. ACR induced also significant changes in zebrafish brain proteome and formed adducts with selected cysteine residues of specific proteins, some of them essential for the presynaptic function. Finally, the metabolomics analysis shows a depletion in the monoamine neurotransmitters, consistent with the comorbid depression and anxiety disorder, in the brain of the exposed fish.
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