Takeda A, Onodera H, Sugimoto A, Kogure K, Obinata M, Shibahara S
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine, Sendai, Japan.
Neuroscience. 1993 Jul;55(1):23-31. doi: 10.1016/0306-4522(93)90451-k.
Changes in nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 messenger RNA expression in the rat hippocampus following 20 min of transient forebrain ischemia were evaluated using Northern blot analysis and in situ hybridization histochemistry. Twelve hours after the insult, the level of nerve growth factor messenger RNA increased markedly in the granular cell layer of the dentate gyrus and by day 2 returned to control levels. The level of brain-derived neurotrophic factor messenger RNA showed a persistent and moderate increase. The highest expression of brain-derived neurotrophic factor messenger RNA was seen in the dentate granule cells on day 2 after the insult, and then the expression returned to the control levels. At 2 days post-ischemia, contents of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor were reduced in the CA1 region, which may represent delayed loss of vulnerable CA1 pyramidal neurons. In contrast to brain-derived neurotrophic factor and nerve growth factor messenger RNA expression, the level of neurotrophin-3 messenger RNA declined in the CA1, the CA2 and the dentate granular layer immediately after ischemic insult. In the CA1 region, the reduced expression persisted for at least seven days, but in the dentate gyrus, neurotrophin-3 messenger RNA expression returned to the control levels after two days of post-ischemic recovery. These results suggest that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 genes are differentially regulated and that each of their gene products may play different roles in the central nervous system under pathophysiological conditions.
运用Northern印迹分析和原位杂交组织化学技术，评估短暂性前脑缺血20分钟后大鼠海马中神经生长因子、脑源性神经营养因子和神经营养素-3信使核糖核酸表达的变化。损伤后12小时，齿状回颗粒细胞层中神经生长因子信使核糖核酸水平显著升高，到第2天恢复至对照水平。脑源性神经营养因子信使核糖核酸水平呈现持续且适度的升高。损伤后第2天在齿状颗粒细胞中可见脑源性神经营养因子信使核糖核酸的最高表达，随后表达恢复至对照水平。缺血后2天，CA1区神经生长因子和脑源性神经营养因子的信使核糖核酸含量降低，这可能代表易损的CA1锥体细胞延迟性丢失。与脑源性神经营养因子和神经生长因子信使核糖核酸表达不同，缺血损伤后即刻，CA1、CA2和齿状颗粒层中神经营养素-3信使核糖核酸水平下降。在CA1区，表达降低至少持续7天，但在齿状回，缺血后恢复2天后神经营养素-3信使核糖核酸表达恢复至对照水平。这些结果表明，神经生长因子、脑源性神经营养因子和神经营养素-3基因受到不同调控，并且在病理生理条件下它们各自的基因产物可能在中枢神经系统中发挥不同作用。
