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

Abstract

Classically, the zebrafish model organism has been used to elucidate the genetic and cellular mechanisms related to development since the embryo forms and grows externally following fertilization. This provides insight into the genetic control of developmental processes in humans because their genomes are similar. Also, unlike other animal models, the genes of zebrafish can be manipulated quite easily by using reverse genetic screens tools such as morpholinos, which transiently silence target genes of interest or systems such as the transposon-mediated insertional mutagenesis or CRISPR-Cas9. Moreover, one pair of fish will provide up to 300 offspring, which means that if there is a gene of interest that is manipulated, then it can be transmitted to a large population of fish. What is beginning to emerge is that similar to other mammals, adult zebrafish have an integrated nervous system, which is proposed to contain homologous brain structures to those found in humans, as well as equivalent cellular and synaptic structure and function. 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 integrity underlie these changes. Therefore, the zebrafish is a powerful model organism for studying the neurobiological consequences of aging-related behavioral and biological changes, which offers the potential to identify possible interventions that would promote healthy aging. In what follows, we present and discuss recent findings and advances along these directions.