ZeTox

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icon-neuro-tox NeuroTox

Exposure to some drugs might alter the normal activity of the nervous system, even promoting an irreversible damage to nervous tissue. Neurotoxicity is remarkably common and among the most frequent reason for drug attrition. Zebrafish behaviors include feeding, seizures, involuntary movement, sleeping, and addiction.

A good example can be found in Lam, 2005. They showed how MPTP specifcally perturbed dopamine transporter (DAT) expressing neurons and also induced deficits in swimming response (3).

Therefore, zebrafish is suitable to both assessing the toxicity of drugs affecting those behaviors and (1) finding novel neuroprotectors (2).

Thanks to DanioVision™ system (Noldus IT) we are capable of measuring locomotor activity in an automated way.

Method description

ZeClinics neurotoxicity assay has been internally validated through the analysis of a 24 compound library (4). Locomotor activity is assessed by altering Light and dark phases during the trial. Alteration in total locomotion and/or its stereotyped pattern suggests a drug-induced neuronal impact.

Readouts

  • Determination of changes on basal locomotor activity and/or stereotyped pattern.
  • The survival of neurons can also be addressed. Transgenic larvae expressing a neuron-specific fluorescent reporter are incubated with the molecule of interest and fixed, after the behavioral test, to allow the quantification of neurons.

References

  1. Parng, C. et al. 2007. Neurotoxicity assessment using zebrafish. J. Pharmacol.Toxicol. Methods.
  2. Kokel D, Bryan J, Laggner C, White R, Cheung CY, et al. 2010. Rapid behavior-based identification of neuroactive small molecules in the zebrafish. Nat. Chem. Biol.
  3. Lam CS, Korzh V and Strahle U. 2005. Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP. Eur. J. Neurosci.
  4. Cornet C, Calzolari S et al. 2017. ZeGlobalTox: an innovative approach to address organ drug toxicity using zebrafish. Int. J. Mol. Sci.  18, 864