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NADH hyperoxidation correlates with enhanced susceptibility of aged rats to hypoxia.
- Foster KA, Margraf RR, Turner DA
Neurobiol Aging. 2006 Dec 19;.
Aging
increases mitochondrial
dysfunction
and susceptibility to hypoxia.
Previous reports have indicated an association between post-hypoxic hyperoxidation of intra-mitochondrial enzymes and delayed neuronal
injury. Therefore we investigated the relationship between NADH fluorescence
and neuronal
function during and after hypoxia
across the lifespan. Hippocampal
slices were prepared from adult (1 to >22 months) F344 rats. NADH fluorescence,
extracellular
voltage
and tissue PO(2) were recorded from the CA1 region during hypoxia
(95% N(2)) of various lengths following onset of hypoxic spreading depression
(hsd). Slices from younger rats recovered evoked neuronal
responses to a greater degree and exhibited less hyperoxidation after a hypoxic episode,
than slices from older rats. However, the use of Ca(2+) free-media in slices from >22 month old rats improved recovery and delayed NADH hyperoxidation (2.5min hypoxia
after hsd). Post-hypoxic decrease of NADH fluorescence
(hyperoxidation) was age dependent and correlated with decreased neuronal
recovery. Slices exposed to repeated hypoxic episodes yielded data suggesting depletion
of the NAD(+) pool, which may have contributed to the deterioration of neuronal
function.
This abstract at PubMed.