BRAIN-DERIVED NEUROTROPHIC FACTOR IS INDUCED AS AN IMMEDIATE-EARLY GENE FOLLOWING N-METHYL-D-ASPARTATE RECEPTOR ACTIVATION

被引:125
作者
HUGHES, P
BEILHARZ, E
GLUCKMAN, P
DRAGUNOW, M
机构
[1] UNIV AUCKLAND, SCH MED, DEPT PHARMACOL & CLIN PHARMACOL, PRIVATE BAG 92019, AUCKLAND, NEW ZEALAND
[2] UNIV AUCKLAND, SCH MED, DEV MED & BIOL RES CTR, AUCKLAND, NEW ZEALAND
关键词
D O I
10.1016/0306-4522(93)90065-N
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
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页码:319 / 328
页数:10
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