Dugich-Djordjevic M M, Ohsawa F, Okazaki T, Mori N, Day J R, Beck K D, Hefti F
Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191, USA.
Neuroscience. 1995 Jun;66(4):861-77. doi: 10.1016/0306-4522(94)00631-e.
Ribonuclease protection analysis and quantitative in situ hybridization histochemistry were used to investigate the coordination and regional expression of catalytic and non-catalytic trkB messenger RNAs in the adult rat hippocampus following systemic kainate-induced seizures. Changes in trkB expression were compared with the messenger RNA expression of its neurotrophic ligands, brain-derived neurotrophic factor and neurotrophin-3. TrkB messenger RNA expression was increased in the dentate granule cells at 1-4 h following the onset of seizures, and returned to control levels 16-24 h thereafter. In addition, seizures also induced expression of trkB messenger RNA in putative non-neuronal cells at four to seven days in the molecular layer of the dentate gyrus and the stratum lacunosum moleculare of the CA1 region. Hybridization with probes specific for the non-catalytic trkB receptor and the catalytic trkB receptor revealed that the increases at four and seven days in the molecular layers of the hippocampus reflected an up-regulation of only the non-catalytic form of the receptor. Furthermore, the neuronal increases observed 1-4 h were due to an up-regulation of both trkB TK- and trkB TK+ messenger RNAs. It was established that systemic administration of kainate increased brain-derived neurotrophic factor messenger RNA levels in the pyramidal and granule cell regions of the hippocampus 1-4 h following the onset of behaviorally manifested seizure activity. Early changes in neuronal expression of trkB TK- and trkB TK+ messenger RNA paralleled changes in brain-derived neurotrophic factor messenger RNA in the dentate granule cell and CA1 pyramidal cell layers, but not in the CA3 subregion. These data suggest that concomitant regulation of brain-derived neurotrophic factor and its cognate receptor may play a role in the selective vulnerability of hippocampal subregions to kainate-induced neuropathology. Furthermore, these data suggest a dual function for trkB receptor expression in the hippocampus following kainate-induced seizures, possibly related to both the plastic and degenerative consequences of seizure induction by kainate.
采用核糖核酸酶保护分析和定量原位杂交组织化学方法，研究全身性海藻酸诱导癫痫发作后成年大鼠海马中催化性和非催化性trkB信使核糖核酸（mRNA）的协调及区域表达。将trkB表达的变化与其神经营养配体脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3）的信使核糖核酸表达进行比较。癫痫发作开始后1至4小时，齿状颗粒细胞中trkB信使核糖核酸表达增加，此后16至24小时恢复到对照水平。此外，癫痫发作还在齿状回分子层和CA1区分子层隙状层中假定的非神经元细胞中，在4至7天时诱导trkB信使核糖核酸表达。用针对非催化性trkB受体和催化性trkB受体的特异性探针杂交显示，海马分子层中4天和7天时的增加仅反映了受体非催化形式的上调。此外，1至4小时观察到的神经元增加是由于trkB TK-和trkB TK+信使核糖核酸均上调。已确定，全身性给予海藻酸在行为表现出癫痫活动开始后1至4小时，会增加海马锥体细胞和颗粒细胞区域中脑源性神经营养因子信使核糖核酸水平。trkB TK-和trkB TK+信使核糖核酸在神经元中的早期变化与齿状颗粒细胞层和CA1锥体细胞层中脑源性神经营养因子信使核糖核酸的变化平行，但在CA3亚区则不然。这些数据表明，脑源性神经营养因子及其同源受体的协同调节可能在海马亚区对海藻酸诱导的神经病理学的选择性易损性中起作用。此外，这些数据表明海藻酸诱导癫痫发作后海马中trkB受体表达具有双重功能，可能与海藻酸诱导癫痫发作的可塑性和退行性后果有关。
