Nicotinamide pre-treatment ameliorates NAD(H) hyperoxidation and improves neuronal function after severe hypoxia.

Journal Article (Journal Article)

Prolonged hypoxia leads to irreversible loss of neuronal function and metabolic impairment of nicotinamide adenine dinucleotide recycling (between NAD(+) and NADH) immediately after reoxygenation, resulting in NADH hyperoxidation. We test whether the addition of nicotinamide (to enhance NAD(+) levels) or PARP-1 inhibition (to prevent consumption of NAD(+)) can be effective in improving either loss of neuronal function or hyperoxidation following severe hypoxic injury in hippocampal slices. After severe, prolonged hypoxia (maintained for 3min after spreading depression) there was hyperoxidation of NADH following reoxygenation, an increased soluble NAD(+)/NADH ratio, loss of neuronal field excitatory post-synaptic potential (fEPSP) and decreased ATP content. Nicotinamide incubation (5mM) 2h prior to hypoxia significantly increased total NAD(H) content, improved neuronal recovery, enhanced ATP content, and prevented NADH hyperoxidation. The nicotinamide-induced increase in total soluble NAD(H) was more significant in the cytosolic compartment than within mitochondria. Prolonged incubation with PJ-34 (>1h) led to enhanced baseline NADH fluorescence prior to hypoxia, as well as improved neuronal recovery, NADH hyperoxidation and ATP content on recovery from severe hypoxia and reoxygenation. In this acute model of severe neuronal dysfunction prolonged incubation with either nicotinamide or PJ-34 prior to hypoxia improved recovery of neuronal function, enhanced NADH reduction and ATP content, but neither treatment restored function when administered during or after prolonged hypoxia and reoxygenation.

Full Text

Duke Authors

Cited Authors

  • Shetty, PK; Galeffi, F; Turner, DA

Published Date

  • February 2014

Published In

Volume / Issue

  • 62 /

Start / End Page

  • 469 - 478

PubMed ID

  • 24184921

Pubmed Central ID

  • 24184921

Electronic International Standard Serial Number (EISSN)

  • 1095-953X

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2013.10.025


  • eng

Conference Location

  • United States