Lindsay De Biase, PhD

Synapse health in cognitive aging: central roles for microglial regulation of extracellular matrix (ECM)

Cognitive decline during aging is tightly linked to changes in the status of synapses, the connections between neurons where information is stored. Yet, the factors that regulate synapse health during aging are not well understood. Microglia are immune-like cells in the brain that respond to infection, disease, and injury. Surprisingly, these cells can also regulate the function and integrity of neuronal synapses. Dr. Biase will investigate the possibility that microglia shape synapse health during aging via modification of the extracellular matrix (ECM). The ECM is a meshwork of proteins and sugars woven tightly around neurons that potently regulates synapse stability. Recent studies and Dr. Biase's preliminary data show that microglia express numerous genes involved in building up and breaking down the ECM and that they can engulf ECM components. Dr. Biase will use multiple technical approaches to elucidate links between microglial-ECM interactions, synapse stability, and cognitive performance in aging mice and rats. The overarching goal is to identify molecular pathways for therapeutic modulation of microglial-ECM interactions to preserve cognition.