Zebrafish – a model organism for studying the neurobiological mechanisms underlying cognitive brain aging and use of potential interventions

摘要

Classically, the zebrafish model organism has been used to elucidate the genetic and cellularmechanisms related to development since the embryo forms and grows externally followingfertilization. This provides insight into the genetic control of developmental processes in humansbecause their genomes are similar. Also, unlike other animal models, the genes of zebrafish canbe manipulated quite easily by using reverse genetic screens tools such as morpholinos, whichtransiently silence target genes of interest or systems such as the transposon-mediated insertionalmutagenesis or CRISPR-Cas9. Moreover, one pair of fish will provide up to 300 offspring, whichmeans that if there is a gene of interest that is manipulated, then it can be transmitted to alarge population of fish. What is beginning to emerge is that similar to other mammals, adultzebrafish have an integrated nervous system, which is proposed to contain homologous brainstructures to those found in humans, as well as equivalent cellular and synaptic structure andfunction. Moreover, like humans, zebrafish exhibit age-related declines in cognitive functions,and a convergence of evidence has indicated that subtle changes in cellular and synaptic integrityunderlie these changes. Therefore, the zebrafish is a powerful model organism for studying theneurobiological consequences of aging-related behavioral and biological changes, which offers thepotential to identify possible interventions that would promote healthy aging. In what follows, wepresent and discuss recent findings and advances along these directions.