Abstract

Zebrafish (Danio rerio) is emerging as an increasingly successful model for translational research on human neurological disorders. In this review, we appraise the high degree of neurological and behavioural resemblance of zebrafish with humans. It is highly validated as a powerful vertebrate model for investigating human neurodegenerative diseases. The neuroanatomic and neurochemical pathways of zebrafish brain exhibit a profound resemblance with the human brain. Physiological, emotional and social behavioural pattern similarities between them have also been well established. Interestingly, zebrafish models have been used successfully to simulate the pathology of Alzheimer’s disease (AD) as well as Tauopathy. Their relatively simple nervous system and the optical transparency of the embryos permit real-time neurological imaging. Here, we further elaborate on the use of recent real-time imaging techniques to obtain vital insights into the neurodegeneration that occurs in AD. Zebrafish is adeptly suitable for Ca2+ imaging, which provides a better understanding of neuronal activity and axonal dystrophy in a non-invasive manner. Three-dimensional imaging in zebrafish is a rapidly evolving technique, which allows the visualisation of the whole organism for an elaborate in vivo functional and neurophysiological analysis in disease condition. Suitability to high-throughput screening and similarity with humans makes zebrafish an excellent model for screening neurospecific compounds. Thus, the zebrafish model can be pivotal in bridging the gap from the bench to the bedside. This fish is becoming an increasingly successful model to understand AD with further scope for investigation in neurodevelopment and neurodegeneration, which promises exciting research opportunities in the future.

Highlights

  • Zebrafish (Danio rerio) is emerging as an increasingly successful model for translational research on human neurological disorders

  • Further studies on the neuronal patterns in the spinal cord of adult zebrafish, neural differentiation and development of spinal network establish their similarity to higher order vertebrates[58,59,60]

  • Cytoskeletal disruption occurred on expressing frontotemporal dementia with Parkinsonism linked to chromosome 17, a mutant form of human Tau in the neurons of the zebrafish, which resembled the neurofibrillary tangles observed in AD100,101

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Summary

Open questions

● Zebrafish can be used as a model to study various disease pathologies in Alzheimer’s disease. ● Laser axotomy coupled with time-lapse imaging and 3D imaging reveal interesting facts about degeneration/regeneration in Zebrafish larvae. ● New approaches to treat Alzheimer’s disease can be further unearthed with this model. ● Can real-time imaging in zebrafish address the major breakthroughs in the field of Alzheimer’s research?. ● Can zebrafish merge the gap between neurospecific drug discovery and clinical research?. Introduction: zebrafish is emerging as a robust model for study of human neurodegeneration. The zebrafish (Danio rerio) is a prominent vertebrate model system for comprehensive analysis of the unique functions of genes along with their signalling pathways during development and neurodegeneration[1].

Official journal of the Cell Death Differentiation Association
Zebrafish as an AD model
Behavioural similarity
Zebrafish as a neuropharmacological model
Zebrafish as neurogenetic model
Findings
Neurospecific drug discovery using zebrafish model
Controversies around the use of zebrafish for research on AD
Scope of research

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