Elaine M. Podosek, Dr Jianxin Bao, Ph.D., Laboratory of Prebyscusis and Aging, Department of Otolaryngology, Center for Aging, Washington University School of Medicine

We all know that as people age, certain abilities are lost. Physically, mentally, age defeats us all. But why does this happen? How is it actually that these capabilities decline with increased age? Specifically in terms of memory loss, this may be related to synapse strength in the brain, with loss of synaptic proteins such as neurotransmitter receptors during age.

To elucidate molecular mechanisms underlying age-related decline of neuronal functions, we have developed transgenic tissue-specific mouse models to study whether Neuregulin-1 (Nrg-1) over-expression can delay age-related memory loss. Nrg-1 belongs to a family of growth factors, which play an important role in the development and maintenance of synaptic connections. Thus, Nrg-1 over-expression could enhance synaptic connections. We specially over-express Nrg-1 in hippocampus neurons, which stores information for spatial learning and memory. The mental abilities of spatial learning and memory were measured in our transgenic mice using a behavior test, the Water Maze, in which mice were to find a submerged platform in opaque water, based on their memory of where it was within the maze. Although the results thus far are not statistically significant between Nrg-1 transgenic mice and control mice, a trend starts to appear for a delay of age-related memory loss in male transgenic mice over-expressing Nrg-1. Further experiments are needed to clearly address our hypothesis in the future.