Hosted by the Tracy Family Stable Isotope Labeling Quantitation (SILQ) Center

SILQ seminars meet on the 2nd Thursday of each month.

Short Bio: Brian Lananna is a postdoctoral scholar studying the neurobiology of aging in the laboratory of Dr. Shin-Ichiro Imai in the department of developmental Biology at Washington University. He earned his PhD in Neurosciences from Washington University in the laboratory of Dr. Erik Musiek where he studied the link between circadian clock dysfunction, astrocyte activation, and Alzheimer’s disease. Dr. Lananna’s current project focuses on the role of extracellular vesicles in the regulation of cognitive aging. Previously, the Imai Lab demonstrated that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the major mammalian NAD+ biosynthesis pathway, is contained in extracellular vesicles (EVs) and secreted to plasma. Treatment of aged mice with plasma-derived EVs containing extracellular NAMPT (eNAMPT) extends mouse lifespan and healthspan. Dr. Lananna has now uncovered converging evidence in Morris Water Maze, Barnes Maze, and novel object location tasks that EV-treatment in 24-month-old mice can rescue age-related deficits in hippocampal-dependent memory and cognitive flexibility. He has used super-resolution synaptic quantification in the same mice to reveal that age-related synapse loss, specifically in the CA1 region of the hippocampus, is largely restored with EV-treatment. Peripherally injected EVs are taken up by a wide variety of tissues. In the brain, EVs are trafficked only to a few specific brain regions including the retrosplenial cortex and hippocampal CA1, which are known to regulate cognition. EV administration also increases NAD+ specifically in these brain regions in old mice. Together, these data suggest that plasma-derived EVs may ameliorate age-related cognitive dysfunction through restoration of hippocampal synaptic density, potentially via NAMPT-dependent replenishment of hippocampal NAD+. Proteomic analysis of EVs across the mouse lifespan as well as single-cell RNAseq analysis of the retrosplenial cortex in EV-treated mice are currently being explored for potential mechanistic insight linking the deterioration of the EV proteome with age to transcriptional changes that may influence the observed behavioral phenotypes. Additionally, this project reveals eNAMPT-containing EVs as a potentially viable biologic to treat cognitive deterioration in aging. In the near future, Dr. Lananna aspires to lead his own academic laboratory in interrogating the fundamental biology integral to ameliorating aging-associated cognitive deterioration.

For inquiries contact Tracy Meier or Chihiro Sato.