BRAIN-DERIVED NEUROTROPHIC FACTOR IS INDUCED AS AN IMMEDIATE-EARLY GENE FOLLOWING N-METHYL-D-ASPARTATE RECEPTOR ACTIVATION
BRAIN-DERIVED NEUROTROPHIC FACTOR IS INDUCED AS AN IMMEDIATE-EARLY GENE FOLLOWING N-METHYL-D-ASPARTATE RECEPTOR ACTIVATION
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DOI：
10.1016/0306-4522(93)90065-n
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发表时间：
1993-11-01
期刊：
影响因子：
3.3
通讯作者：
DRAGUNOW, M
中科院分区：
文献类型：
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作者：
HUGHES, P;BEILHARZ, E;DRAGUNOW, M
近年来的研究表明，局灶性脑损伤、脑缺血、低血糖和癫痫等均可引起脑内c-fos和脑源性神经营养因子表达增加。在这里，我们报告海马局灶性脑损伤瞬时诱导大鼠齿状回神经元的即刻早期基因c-fos，jun -B，c-jun和krox-24（zif-268）信使RNA和蛋白质以及脑源性神经营养因子信使RNA，这种作用被N-甲基-D-天冬氨酸受体拮抗剂MK-801阻断。预先给予蛋白质合成抑制剂放线菌酮可超诱导即刻早期基因信使RNA，消除即刻早期基因蛋白诱导，但对损伤介导的脑源性神经营养因子信使RNA的诱导没有影响。因此，虽然N-甲基-D-天冬氨酸受体激活导致即刻早期基因和脑源性神经营养因子信使RNA的诱导，即时早期基因蛋白的从头合成对于局灶性损伤后脑中所见的脑源性神经营养因子信使RNA的表达增加并不关键。这些结果表明，脑源性神经营养因子作为一个立即早期基因在损伤后被诱导。
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.