In Vivo MR Study of Intracellular NAD Contents and Redox State in Healthy Human Brain

Xiao-Hong Zhu¹, Ming Lu¹, Byeong-Yeul Lee¹, Kamil Ugurbil¹, Wei Chen²

Intracellular NAD (nicotinamide adenine dinucleotide) concentrations and redox state (define as the ratio between oxidized and reduced NAD) have been closely linked to the energy production, metabolic regulation and signal transduction processes occur in all living cells. Thus, the ability to study the intracellular NAD contents and redox state is essential for understanding their pivotal roles in brain function and dysfunctions. Despite the importance, however, the level of NAD or its redox ratio in normal human brain is virtually unknown because the lack of proper tools for in vivo measurements. In this study, we applied a novel ³¹P MRS approach recently developed in our lab to directly measure the NAD contents and the NAD⁺/NADH redox ratio in healthy human brains at 7T. The results reveal, for the first time, that i) it is feasible to robustly measure and identify the MRS signals of NAD⁺ and NADH in the human brain; ii) the knowledge regarding the NAD and its redox state in human brain can be readily and non-destructively obtained; and iii) age-dependent changes exist in the intracellular NAD concentrations and NAD⁺/NADH redox states of the healthy human brains. This work presents a MR technology breakthrough and provides new opportunities for studying the central roles of the NAD and its redox in human health and diseases.