DIFFERENTIAL REGULATION OF MESSENGER-RNAS FOR NERVE GROWTH-FACTOR, BRAIN-DERIVED NEUROTROPHIC FACTOR, AND NEUROTROPHIN-3 IN THE ADULT-RAT BRAIN FOLLOWING CEREBRAL-ISCHEMIA AND HYPOGLYCEMIC COMA
DIFFERENTIAL REGULATION OF MESSENGER-RNAS FOR NERVE GROWTH-FACTOR, BRAIN-DERIVED NEUROTROPHIC FACTOR, AND NEUROTROPHIN-3 IN THE ADULT-RAT BRAIN FOLLOWING CEREBRAL-ISCHEMIA AND HYPOGLYCEMIC COMA
复制标题
DOI：
10.1073/pnas.89.2.648
复制
发表时间：
1992-01-15
影响因子：
11.1
通讯作者：
PERSSON, H
中科院分区：
文献类型：
--
作者：
LINDVALL, O;ERNFORS, P;PERSSON, H
采用原位杂交技术研究大鼠前脑缺血2 min和10 min以及胰岛素诱导的低血糖昏迷1 min和30 min后神经生长因子（NGF）家族成员mrna的表达。缺血2 h后，齿状回颗粒细胞脑源性神经营养因子（BDNF） mRNA水平显著升高，24 h时仍显著升高。NGF mRNA在缺血2分钟后4小时显著升高，但在缺血24小时后恢复到对照水平。缺血2和10分钟均导致海马齿状颗粒细胞和海马CA2区和内侧CA1区神经营养因子3 (NT-3) mRNA水平在缺血2和4小时后明显降低。α -氨基-3-羟基-5-甲基-4-异恶唑烯丙酸（AMPA）受体拮抗剂NBQX可部分阻断BDNF mRNA的表达，而n -甲基- d -天冬氨酸（NMDA）受体拮抗剂MK-801对BDNF mRNA表达无影响。NBQX和MK-801均能减轻缺血后NT-3 mRNA的减少。1分钟和30分钟的低血糖昏迷也诱导齿状颗粒细胞中BDNF和NGF mRNA的显著增加，并在2小时达到最高水平。如果mRNA表达的变化导致神经营养因子的相对可用性改变，这可能影响缺血和低血糖损伤后的功能结局和神经元坏死。
In situ hybridization was used to study expression of mRNAs for members of the nerve growth factor (NGF) family in the rat brain after 2 and 10 min of forebrain ischemia and 1 and 30 min of insulin-induced hypoglycemic coma. Two hours after the ischemic insults, the level of brain-derived neurotrophic factor (BDNF) mRNA was markedly increased in the granule cells of the dentate gyrus, and at 24 h it was still significantly elevated. NGF mRNA showed a pronounced increase 4 h after 2 min of ischemia but had returned to a control level at 24 h. Both 2 and 10 min of ischemia caused a clear reduction of the level of mRNA for neurotrophin 3 (NT-3) in the dentate granule cells and in regions CA2 and medial CA1 of the hippocampus 2 and 4 h after the insults. The increase of BDNF mRNA could be partially blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX but was not influenced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Both NBQX and MK-801 attenuated the decrease of NT-3 mRNA after ischemia. One and 30 min of hypoglycemic coma also induced marked increases in BDNF and NGF mRNA in dentate granule cells with maximal levels at 2 h. If the changes of mRNA expression lead to alterations in the relative availability of neurotrophic factors, this could influence functional outcome and neuronal necrosis following ischemic and hypoglycemic insults.