Regulation of brain energy metabolism by NAD and sirtuins

All cells require a constant supply of energy to survive, however the active and dynamic environment within the brain imposes not only a high basal energy requirement, but also vastly fluctuating energy demands across the course of a normal day. Fundamental to understanding brain energy metabolism is the lynchpin molecule, nicotinamide adenine dinucleotide (NAD). Despite its central importance to brain metabolism, we still do not know how the fundamental processes of NAD synthesis, recycling and catabolism are regulated in brain.  Through use of highly innovative and novel strategies combining new molecular tools and flagship infrastructure, we are selectively dissecting the synthesis and roles of NAD across the 3 major classes of neural cells – neurons, astrocytes, oligodendrocytes. The results of this project will generate a systems biology platform to underpin manipulations of NAD homeostasis as well as to understand the relationship between brain NAD levels and mitochondrial function.

Main Collaborators: Gary Housley (SOMS), Matthias Klugmann (SOMS), Ben Rowlands (NeuRA)

Rowlands, B., Klugmann, M & Rae, C.D. (2017) Acetate metabolism does not reflect astrocytic activity, contributes directly to GABA synthesis, and is increased by silent information regulator 1 activation. The Journal of Neurochemistry  140, 903-918.