Research in our laboratory primarily focuses on understanding the cellular and synaptic changes in the aging brain that may be contributing to age-related cognitive decline. Some of the questions that we are interested in are the following: What are the specific changes that take place during aging which lead to decrements in neural function? What are the intrinsic biological determinants of those changes? What factors can ameliorate these changes?
To this end we are utilizing the zebrafish as a model organism. The appeal of the zebrafish as a potential model of aging and other age-associated diseases such as Alzheimer’s disease recently has come into favour. This is due to the large amount of information on zebrafish development, molecular biology and genetics, as well as successful large-scale mutagenesis programs and the availability of multiple mutant and transgenic phenotypes, zebrafish are uniquely suitable for studying genetic and early developmental factors that affect the aging process in vertebrates. Moreover, research aimed at examining aging effects in zebrafish behavior indicates that these animals exhibit a gradual decline in learning and memory, similar to that observed in humans. Currently we are examining the effects of dietary restriction on the cognitive and biological aging. Caloric restriction is the only known non-genetic intervention that reliably increases lifespan and healthspan. The primary significance of this research is in understanding the cellular mechanisms through which caloric restriction acts in order to develop potential mimetics.
A parallel area of research in our laboratory investigates the cellular and synaptic changes that contribute to neurodevelopmental disorders such as mental retardation. We are using morpholinos in zebrafish embryos to knockdown genes that are associated with different developmental disorders. We can then follow the progression of brain development in the absence of the genes to determine the progression of cellular and synaptic alterations. These data will provide targets that could be rescued in order to prevent the development of these disorders.