Dataset Information

Modeling acrylamide acute neurotoxicity in zebrafish larvae

ABSTRACT: Background: Acrylamide (ACR) is a broadly spread neurotoxic chemical of public health concern, as occupational or environmental exposure of humans to ACR may lead to a synaptopathy characterized by ataxia, skeletal muscles weakness and numbness of the extremities. Currently, only the mildly affected patients undergo complete recovery, and identification of new molecules with therapeutic bioactivity against ACR acute neurotoxicity is urgently needed. Objectives: We aimed to develop a zebrafish model for human ACR neurotoxicity. Methods: Adverse effects have been assessed at different levels, including analysis of the motor function (basal locomotor activity, visual motor response, kinematic of the touch-evoked escape response), histopathological evaluation (toluidine blue and whole-mount immunofluorescence), analysis of neural transcriptional markers (qPCR), proteomic analysis (μLC-MS-MS) and neurotransmitters profile (LC-MS/MS). Results: Our results show that zebrafish mimics most of the pathophysiological processes described in humans and mammalian models. Motor function was altered, including the response to sudden changes in light intensity. 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 found on cholinergic and dopaminergic systems. Conclusions: Thus, the zebrafish model for ACR acute neurotoxicity is suitable to be used larvae for in vivo high-throughput screening of small molecule libraries for identifying new drugs against this synaptopathy.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Danio Rerio (zebrafish) (brachydanio Rerio)

SUBMITTER: Tamar Ziv

LAB HEAD: Demetrio Raldúa

PROVIDER: PXD007169 | Pride | 2018-10-24

REPOSITORIES: Pride

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Modelling acrylamide acute neurotoxicity in zebrafish larvae.

Prats Eva E Gómez-Canela Cristian C Ben-Lulu Shani S Ziv Tamar T Padrós Francesc F Tornero Daniel D Garcia-Reyero Natàlia N Tauler Romà R Admon Arie A Raldúa Demetrio D

Scientific reports 20171024 1

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 m ...[more]

PMID: 29066856

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