Modelling acrylamide acute neurotoxicity in zebrafish larvae
Prats, Eva (CID-CSIC)
Gómez-Canela, Cristian (IDAEA-CSIC)
Ben-Lulu, Shani (Technion - Israel Institute of Technology)
Ziv, Tamar (Technion - Israel Institute of Technology)
Padrós, Francesc 1965- (Universitat Autònoma de Barcelona. Servei de Diagnòstic Patològic en Peixos)
Tornero, Daniel (IDAEA-CSIC)
Garcia-Reyero, Natàlia (Environmental Laboratory-US Army Engineer Research and Development Center)
Tauler, Romà (IDAEA-CSIC)
Admon, Arie (Technion - Israel Institute of Technology)
Raldúa, Demetrio (IDAEA-CSIC)

Fecha:	2017
Resumen:	Acrylamide (ACR), a type-2 alkene, may lead to a synaptopathy characterized by ataxia, skeletal muscles weakness and numbness of the extremities in exposed human and laboratory animals. Currently, only the mildly affected patients undergo complete recovery, and identification of new molecules with therapeutic bioactivity against ACR acute neurotoxicity is urgently needed. Here, we have generated a zebrafish model for ACR neurotoxicity by exposing 5 days post-fertilization zebrafish larvae to 1 mM ACR for 3 days. Our results show that zebrafish mimics most of the pathophysiological processes described in humans and mammalian models. Motor function was altered, and specific effects were found on the presynaptic nerve terminals at the neuromuscular junction level, but not on the axonal tracts or myelin sheath integrity. Transcriptional markers of proteins involved in synaptic vesicle cycle were selectively altered, and the proteomic analysis showed that ACR-adducts were formed on cysteine residues of some synaptic proteins. Finally, analysis of neurotransmitters profile showed a significant effect on cholinergic and dopaminergic systems. These data support the suitability of the developed zebrafish model for screening of molecules with therapeutic value against this toxic neuropathy.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Scientific reports, Vol. 7 (october 2017) , ISSN 2045-2322

DOI: 10.1038/s41598-017-14460-3
PMID: 29066856

12 p, 1.9 MB

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