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NADH hyperoxidation correlates with enhanced susceptibility of aged rats to hypoxia.

Abstract
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 (2.5 min 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.
AuthorsKelley A Foster, Russell R Margraf, Dennis A Turner
JournalNeurobiology of aging (Neurobiol Aging) Vol. 29 Issue 4 Pg. 598-613 (Apr 2008) ISSN: 1558-1497 [Electronic] United States
PMID17184883 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • NAD
Topics
  • Aging (metabolism)
  • Animals
  • Calcium Signaling (physiology)
  • Cell Hypoxia (physiology)
  • Cell Survival (physiology)
  • Disease Susceptibility
  • Excitatory Postsynaptic Potentials (physiology)
  • Hippocampus (metabolism)
  • Hypoxia, Brain (metabolism)
  • NAD (metabolism)
  • Organ Culture Techniques
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred F344

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