Brain-derived neurotrophic factor is induced as an immediate early gene following N-methyl-D-aspartate receptor activation

Neuroscience. 1993 Nov;57(2):319-28. doi: 10.1016/0306-4522(93)90065-n.


Recent studies show that focal brain injury, cerebral ischaemia, hypoglycaemia and seizures increase the expression of c-fos and brain-derived neurotrophic factor in brain. Here we report that hippocampal focal brain injury transiently induces the immediate early genes c-fos, jun-B, c-jun and krox-24 (zif-268) messenger RNA and protein and brain-derived neurotrophic factor messenger RNA in rat dentate gyrus neurons, an effect that was blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Prior administration of the protein synthesis inhibitor cycloheximide super-induced immediate early gene messenger RNA, abolished immediate early gene protein induction, but had no effect on injury-mediated induction of brain-derived neurotrophic factor messenger RNA. Thus, while N-methyl-D-aspartate receptor activation results in the induction of both immediate early genes and brain-derived neurotrophic factor messenger RNA, de novo synthesis of immediate early gene proteins is not critical for the increased expression of brain-derived neurotrophic factor messenger RNA seen in brain after focal injury. These results suggest that brain-derived neurotrophic factor is induced after injury as an immediate early gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / metabolism
  • Brain-Derived Neurotrophic Factor
  • Cycloheximide / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Gene Expression / drug effects
  • Genes, Immediate-Early / physiology*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Nerve Tissue Proteins / biosynthesis*
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*


  • Brain-Derived Neurotrophic Factor
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Cycloheximide