Pushkar Kulkarni, M.V.M.
Zebrafish Models for Drug Discovery of Neurodegenerative Disorders
Education & Training
2005 : M.V. M. (Tox.) Swedish University of Agricultural Sciences, Uppsala, Sweden.
2006 –2009: Research Scientist, Drug Safety Evaluation, Ranbaxy Labs. Ltd., Gurgaon.
2009 –2010: Associate Scientist, Pharmacology & Toxicology, GVK BIO, Hyderabad.
2010 Onwards: Institute of Life Sciences, Hyderabad, India.
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons.. Inflammation and stress plays a major role in the pathophysiology of neurodegenerative diseases. Brain derived Neurotrophic Factor (BDNF) plays a central role in synaptic plasticity and neuronal survival. It is considered as an important candidate gene in most neurogenerative diseases as per the “neurotrophin hypothesis”.
Zebrafish (Danio rerio) have emerged as a useful in vivo model organism to study the effects of chemicals and pharmaceuticals. Zebrafish models have are being increasingly being used in the field of neurobiology, neuropharmacology and neurotoxicology. Recent reviews suggest that zebrafish models compare strongly to parallel animal and clinical evidence with respect to models of neurosciences.
Our laboratory at the Institute of Life Sciences, Hyderabad is the first laboratory to develop a method for conducting oral dosing and blood brain barrier permeability (BBB) experiments in adult zebrafish. This allows delivering specific amounts of chemicals to adult zebrafish and which is non-traumatic, painless and ethical method of oral administration. Thus we can conduct various zebrafish based assays and ascertain the dose of pharmacological agents in terms of milligram per kilogram. This evaluation along with literature based data on higher mammals and humans shall allow us to develop an extrapolation factor of drug dose from zebrafish to rodents and humans. A model shall be evolved to predict neurodegeneration and behavioral effects based on the thresholds of inflammatory markers and BDNF expression together. This information shall ultimately help identify both biomarkers as well as therapeutic targets for various neurodegenerative diseases.