BRAIN INSULTS IN RATS INDUCE INCREASED EXPRESSION OF THE BDNF GENE THROUGH DIFFERENTIAL USE OF MULTIPLE PROMOTERS
BRAIN INSULTS IN RATS INDUCE INCREASED EXPRESSION OF THE BDNF GENE THROUGH DIFFERENTIAL USE OF MULTIPLE PROMOTERS
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DOI：
10.1111/j.1460-9568.1994.tb00303.x
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发表时间：
1994-04-01
影响因子：
3.4
通讯作者：
LINDVALL, O
中科院分区：
文献类型：
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作者：
KOKAIA, Z;METSIS, M;LINDVALL, O
大鼠脑源性神经营养因子 (BDNF) 基因由连接到单独启动子的四个短 5' 外显子和一个编码成熟 BDNF 蛋白的 3' 外显子组成。使用原位杂交，我们在此证明，引火诱发的癫痫发作、脑缺血和胰岛素诱发的低血糖昏迷通过对 BDNF 基因内的三个启动子进行损伤和区域特异性使用来增加 BDNF mRNA 水平。短暂（2 分钟）和较长（10 分钟）的前脑缺血仅诱导齿状回中外显子 III mRNA 的显着且大幅增加。低血糖昏迷后（1 分钟和 30 分钟），齿状回中外显子 III mRNA 显着升高，此外，外显子 I mRNA 显示中度升高。单次和反复 (n = 40) 海马癫痫发作显着增加齿状回颗粒细胞中外显子 I、II 和 III mRNA 的表达。反复发作（包括全身惊厥）后，CA3 区、杏仁核、梨状皮层和新皮质中的外显子 I 和 III mRNA 也显着增加，而在海马 CA1 区，仅检测到外显子 III mRNA 显着升高。这些侮辱对大脑中外显子 IV mRNA 的水平没有影响。启动子激活的区域和损伤特异性模式可能对于保护反应的有效性以及脑损伤后塑性变化的调节很重要。
The rat brain-derived neurotrophic factor (BDNF) gene consists of four short 5'-exons linked to separate promoters and one 3'-exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate here that kindling-induced seizures, cerebral ischaemia and insulin-induced hypoglycaemic coma increase BDNF mRNA levels through insult- and region-specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent (n = 40) hippocampal seizures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, including generalized convulsions, there were also major increases of both exon I and III mRNAs in the CA3 region, amygdala, piriform cortex and neocortex, whereas in the hippocampal CA1 sector marked elevations were detected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region- and insult-specific pattern of promoter activation might be of importance for the effectiveness of protective responses as well as for the regulation of plastic changes following brain insults.