Niacinamide blocks 3-acetylpyridine toxicity of cerebellar granule cells in vitro

Michael Weller, Ann M. Marini, Steven M. Paul

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

3-Acetylpyridine (3AP) is a potent neurotoxin when administered to laboratory animals. However, its neurotoxic effects have not been investigated extensively in vitro. Cultured cerebellar granule cells are killed by concentrations of 3AP of 0.1-1 mM (ED50 = 220 μM) but not by its 2-acetyl and 4-acetyl analogues. The toxicity of 3AP is enhanced by preexposure to subtoxic concentrations of N-methyl-d-aspartate (NMDA) and is unaffected by the NMDA receptor antagonists MK-801 or APV, as well as by deprenyl, mazindol, or tetrahydrofolic acid. However, 3AP toxicity is completely blocked by preincubating cerebellar granule cells with low concentrations of niacinamide. These data lead us to suggest that 3AP toxicity is due to the substitution of 3AP for niacinamide in the formation of niacinamide adenine dinucleotides (NAD(P)).

Original languageEnglish
Pages (from-to)160-164
Number of pages5
JournalBrain Research
Volume594
Issue number1
DOIs
StatePublished - Oct 23 1992

Keywords

  • 3-Acetylpyridine
  • Cerebellar granule cell
  • Neurotoxicity
  • Niacinamide

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