Acrylamide acute neurotoxicity in adult zebrafish

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. © 2018 The Author(s).We thank Prof. Allan V. Kalueff, from the Institute of Translational Biomedicine (Saint-Petersburg State University, Russia), for his comments and suggestions on the behavioral analysis results, and to Marc Mañas, from CID-CSIC, for his technical support in the development of the NTT and OFT setups. Tis work was supported in part by the NATO SfP project MD.SFPP 984777 (D.R., A.A.), the Advanced Grant ERC-2012-AdG-320737 (D.R., B.P., C.G.-C., R.T.), the Spanish Government (CTM2017-83242-R; D.R.) and the I-CORE Program of the Planning and Budgeting Committee and Te Israel Science Foundation (grant No. 1775/12 to A.A.) for the purchase of the mass spectrometer. M.F acknowledges fnancial support from the Beatriu de Pinós programme (grant No. 2016 BP 00233) provided by the Secretariat of Universities and Research department of the Ministry for Business and Knowledge, Catalonia Government. K.A.N.L was supported by a grant (291212) from the Mixed Fund programme for mobility (CONACYT-2017).Peer reviewe