MSTP in PhD Training
Current advisor: Shin-ichiro Imai, MD, PhD
Undergraduate university: Cornell University, 2016
Enrollment year: 2019
Investigating the role of Slc12a8 in aging, neuronal metabolism, and age-associated cognitive decline
Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite for cellular function and bioenergetics. Brain NAD+ levels are known to decrease during aging, while boosting cellular NAD+ via administration of NAD+ precursors ameliorates age-dependent pathologies and metabolic changes associated with NAD+ decline. Of particular interest is nicotinamide mononucleotide (NMN), which is taken up by cells via its transporter Slc12a8. Repletion of NAD+ through NMN supplementation is known to counteract age-associated functional and structural changes seen in healthy brain aging and neurodegenerative disease. However, the role of Slc12a8 in modulating brain NAD+ metabolism is poorly understood. Expression of Slc12a8 is not uniformly distributed in the brain; rather, we have identified a subpopulation of neurons in the lateral septum that highly express Slc12a8 and show decreased neuronal activity during aging. We also observe that Slc12a8 deficient mice show deficits in learning and memory. Together, this suggests a role for Slc12a8 and NMN in the maintenance of memory and other high order cognitive functions. In this work, we characterize the metabolic and transcriptomic profiles of Slc12a8+ neurons, explore their role in modulating brain NAD+ metabolism, and investigate the potential of Slc12a8 as a target for ameliorating age-associated physiological and cognitive decline.