DIFFERENTIAL REGULATION OF CATALYTIC AND NONCATALYTIC TRKB MESSENGER-RNAS IN THE RAT HIPPOCAMPUS FOLLOWING SEIZURES INDUCED BY SYSTEMIC ADMINISTRATION OF KAINATE

被引:42
作者
DUGICHDJORDJEVIC, MM
OHSAWA, F
OKAZAKI, T
MORI, N
DAY, JR
BECK, KD
HEFTI, F
机构
[1] UNIV SO CALIF,ETHEL PERCY ANDRUS GERONTOL CTR,LOS ANGELES,CA 90089
[2] UNIV SO CALIF,DEPT BIOL SCI,LOS ANGELES,CA 90089
关键词
D O I
10.1016/0306-4522(94)00631-E
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 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.
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页码:861 / 877
页数:17
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