Brain-derived neurotrophic factor is induced as an immediate early gene following N-methyl-D-aspartate receptor activation.
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.
Hughes
P
P
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
Beilharz
E
E
Gluckman
P
P
Dragunow
M
M
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor; D003513:Cycloheximide / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003513:Cycloheximide