Further characterization of the zebrafish model of acrylamide acute neurotoxicity: gait abnormalities and oxidative stress
Occupational, accidental, or suicidal exposure to acrylamide (ACR) may result in a neurotoxic syndrome. Development of animal models of acrylamide neurotoxicity is necessary for increasing our mechanistic understanding of this syndrome and developing more effective therapies. A new model for acute ACR neurotoxicity has been recently developed in adult zebrafish. Whereas the results of the initial characterization were really promising, a further characterization is needed for testing the construct validity of the model. In this study, the presence of gait abnormalities has been investigated by using ZebraGait, software specifically designed to analyze the kinematics of fish swimming in a water tunnel. The results of the kinematic analyses demonstrated that the model exhibits mild-to-moderate gait abnormalities. Moreover, the model exhibited negative scototaxis, a result confirming a phenotype of anxiety comorbid with depression phenotype. Interestingly, depletion of the reduced glutathione levels was found in the brain without a concomitant increase in oxidative stress. Finally, hypolocomotion and positive geotaxis exhibited by this model were fully recovered 5 days after transferring the fish to clean fish-water. All this data support the validity of the ACR acute neurotoxicity model developed in adult zebrafish. ; We thank Dr. Caio Maximino, from the Universidade Federal do Sul e Sudeste do Pará (Marabá, Brazil), for his comments and suggestions on the DLT. The IRI Lab technical staff members are gratefully thanked for their valuable assistance in the design of the experimental setup for video-recording the fish swimming. This work was supported by the NATO SfP project MD. SFPP 984777 (D.R.) and the Spanish Government (CTM2017-83242-R; D.R. and J.M.P.). M.F. acknowledges financial 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. ; Peer reviewed