Throughout the past 25 years, there has been commendable progress in neuroscience; utilization of animal models to study the pathophysiology of neurological disorders has been instrymental in research efforts to further understanding of and improve prevention, diagnosis and treatment of neurological disorders. Most of the over 600 known neurological diseases, however, remain incurable with treatment options being limited and up to 1 billion sufferers around the world. For more than a century, rodents have been the most prominently used animal models and have been instrumental in the development of drugs for several neurological diseases. Conversely, rodents also have several shortcomings as animal models for diseases: sparking ethical conflict and proving not the most economically efficient. Recently, other ‘novel model organisms’ such as zebrafish have become an increasingly popular choice amongst researchers due to their numerous benefits and surprisingly high degree of functional homology to humans. There are already examples of zebrafish successfully aiding in the exploration of the underlying genetic mechanisms of epilepsy, Alzheimer’s disease, schizophrenia, Parkinson’s disease (PD) and affective disorders, thus demonstrating their practicality as animal models of neurological diseases.
PD is the second most prevalent progressive neurodegenerative disorder, affecting approximately 1% of those over 60. Around 15% of sufferers have a family history of PD; however, most instances of PD are sporadic. Investigations into hereditary PD alongside animal testing have led to 5 mutated genes being associated with PD’s pathogenesis: LRRK2, SNCU, PRKN, PINK1 and PARK7.
Over the past several decades, various PD animal models have provided considerable insight into PD’s elusive etiology and pathophysiology. Rat models of rotenone, for example, have displayed several features of PD, including intracellular inclusions that resemble LBs and the main neuropathological hallmark: nigrostriatal dopamine depletion (DAd). These rotenone experiments indicate that environmental neurotoxins are involved in the pathogenesis of PD. Neurological and symptomatic treatments (i.e. physical therapy and deep brain stimulation) exist; however, there is currently no cure. As PD can be debilitating, more research in hope of a cure is urgently required.
Zebrafish have already proved useful in modelling several complex neurological disorders such as PD and are rapidly emerging as key organisms in translational neuroscience and biopsychiatry research. Their suitability for high-throughput screening tests also makes them ideal for toxicology studies, thus possibly providing new treatments and even cures for several brain disorders in the future.
Zebrafish’s surprising advantages far outweigh their inevitable shortcomings as animal models and, although already being utilised, possess further potential in terms of enabling incremental neurological discovery in the future. Thus, a fish could feasibly save the brain.
Stella Ezemuo
St Peter’s RC High School, Manchester