Abstract #3778
In Vivo 31 P MRS Study of Altered Intracellular NAD Content and NAD + /NADH Redox State in Hypoxic Brain
Ming Lu 1 , Xiao-Hong Zhu 1 , Yi Zhang 1 , and Wei Chen 1
1
Center for Magnetic Resonance Research,
University of Minnesota Medical School, Minneapolis,
Minnesota, United States
Nicotinamide adenine dinucleotide (NAD) participates in
various redox reactions in living organisms for
supporting normal cellular functions and activities. The
reduced (NADH) and oxidized (NAD
+
) forms of
NAD play key roles in cellular metabolism and
regulation. The intracellular NAD
+
/NADH
ratio, defined as intracellular redox state, reflects
metabolic status and has been found to be associated
with alterations in physiology and pathology. However,
direct quantification of NAD and redox state
in
vivo
is
challenging. In this study, using our newly developed
in
vivo
31
P
MRS approach for imaging NAD and its redox state in
animal brains at 16.4 T, alterations of the NAD
concentrations and redox state in rat brains from
normoxia to hypoxia were studied. When reducing the
oxygen supply from 30~40% (of O
2
and
N
2
O mixture) to 5~6% level, the results
indicated an increase of NADH contents (+25%), and
decreases of [NAD
+
] (-26%), NAD
+
/NADH
ratio (-43%) and total [NAD] (-13%). Also, there were
further increase of [NADH] and decreases of [NAD
+
],
NAD
+
/NADH ratio and total [NAD] in the
postmortem brains. In summary, by using the novel
31
P
MRS method, changes of cerebral redox state and the
intracellular NAD contents can be robustly and
non-invasively quantified under normal and hypoxic
conditions. This simple and highly applicable MR imaging
approach has a great potential for studying metabolic
disorders in different organs of patients with hypoxic
or ischemic syndrome.
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