Suchergebnisse

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. © 2017 The Author(s). ; We thank Dr. Harold A. Burgess for providing Flote software and advice with the kinematic analysis. The 3A10 antibody, developed by Jessell, T.M./Dodd, J./Brenner-Morton, S. (DSHB Hybridoma Product 3A10), was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. This work was supported in part by the NATO SfP project MD.SFPP 984777 (D.R., A.A. and N.G.R.), the US Army Environmental Quality and Installations Research Program (N.G.R.), the Advanced Grant ERC-2012-AdG-320737 (D.R., C.G-C, R.T.), the Spanish Government (CTM2014-51985-R; D.R.) and the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grant No. 1775/12 to A.A.) for the purchase of the mass spectrometer. ; Peer reviewed