Kokaia Z, Kelly M E, Elmer E, Kokaia M, McIntyre D C, Lindvall O
Department of Neurology, University Hospital, Lund, Sweden.
Neuroscience. 1996 Nov;75(1):197-207. doi: 10.1016/0306-4522(96)00257-6.
Levels of messenger RNAs for brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3, and their high-affinity receptors, TrkB and TrkC, were analysed in the brains of genetically fast and slow kindling rats using in situ hybridization. Basal expression of neurotrophins and Trk messenger RNAs in the hippocampal formation, amygdala, frontoparietal and piriform cortices did not differ between the two strains. At 2 h after the third generalized grade 5 seizure, induced by kindling stimulations in the amygdala, increased expression of brain-derived neurotrophic factor messenger RNA was detected in the dentate gyrus granule cell layer, amygdala, frontoparietal and piriform cortices of the fast kindlers. Similar seizure-evoked increases of brain-derived neurotrophic factor messenger RNA levels were also observed in the amygdala and piriform cortex of slow kindlers. However, in these animals, brain-derived neurotrophic factor messenger RNA expression was not significantly altered by the seizures in the dentate gyrus granule cell layer and frontoparietal cortex. Furthermore, the seizure-induced increase of nerve growth factor, TrkB and TrkC messenger RNAs and decrease of neurotrophin-3 messenger RNA levels in the dentate gyrus granule cell layer was only observed in fast, but not in slow, kindlers. The neurotrophins are believed to regulate synaptic plasticity and efficacy and to facilitate long-term potentiation and kindling epileptogenesis. The present data suggest that the slow and fast kindling rates in the two strains studied here might partly be due to differences in seizure-evoked neurotrophin and Trk synthesis.
采用原位杂交技术,分析了基因快速点燃和慢速点燃大鼠大脑中脑源性神经营养因子、神经生长因子和神经营养素-3及其高亲和力受体TrkB和TrkC的信使核糖核酸水平。两品系大鼠海马结构、杏仁核、额顶叶和梨状皮质中神经营养因子和Trk信使核糖核酸的基础表达无差异。在杏仁核点燃刺激诱发第三次全身性5级癫痫发作2小时后,在快速点燃大鼠的齿状回颗粒细胞层、杏仁核、额顶叶和梨状皮质中检测到脑源性神经营养因子信使核糖核酸表达增加。在慢速点燃大鼠的杏仁核和梨状皮质中也观察到类似的癫痫诱发的脑源性神经营养因子信使核糖核酸水平升高。然而,在这些动物中,齿状回颗粒细胞层和额顶叶皮质中的癫痫发作并未显著改变脑源性神经营养因子信使核糖核酸的表达。此外,仅在快速点燃大鼠而非慢速点燃大鼠的齿状回颗粒细胞层中观察到癫痫诱发的神经生长因子、TrkB和TrkC信使核糖核酸增加以及神经营养素-3信使核糖核酸水平降低。神经营养因子被认为可调节突触可塑性和效能,并促进长时程增强和点燃癫痫发生。目前的数据表明,这里研究的两品系大鼠的慢速和快速点燃率可能部分归因于癫痫诱发的神经营养因子和Trk合成的差异。