Abstract

Compatible Changes of Lead microRNAs in Circulating Plasma and Brain in Senescence-Accelerated Aging and Alzheimer's disease Mouse Models

Shephali Bhatnagar, Gregory J. Weber, Vikranth Shetty, Viktoriya Shekhovtsova and Eugenia Wang

Circulating microRNAs have recently emerged as powerful biomarkers because of their potential for monitoring changes in tissues such as the brain during aging. These microRNAs are found in many types of body fluids, and serve not only as systemic indicators of global and tissue-specific changes of gene expression, but also as functional mediators for cell-cell communication. In an effort to link changes in circulating microRNAs to changes in tissue, we used survival bleeding to perform comparative studies of three selected microRNAs, miR-34a, -34c, and -181b, in plasma and brain tissue in two types of animal models, Alzheimer’s Disease (AD) transgenic mutants and Senescence-Accelerated (SAMP8) mice. In this study, we show that expression of these microRNAs is altered in both AD and SAMP8 models, with comparable changes in expression of these specific microRNAs in both plasma and brain, and perhaps earlier in plasma. Our results demonstrate that the survival bleeding method allows longitudinal studies of changes in circulating microRNAs, which can be used as minimally invasive biomarkers of degenerative changes in mouse brain.