Canals J M, Checa N, Marco S, Michels A, Pérez-Navarro E, Alberch J
Departament de Biologia Cel.lular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, IDIBAPS, Casanova 143, 08036, Barcelona, Spain.
Brain Res Mol Brain Res. 1999 Jun 8;69(2):242-8. doi: 10.1016/s0169-328x(99)00130-8.
In the present work, we examined the time-dependent changes in trkA, trkB and trkC mRNA levels induced by the injection of glutamate receptor agonists into the striatum. Changes in trk mRNAs induced by quinolinate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate or 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) were analyzed by a ribonuclease protection assay. All high-affinity neurotrophin receptors showed differential regulation after intrastriatal injury. Up-regulation of trkA expression was observed in kainate- or ACPD-injected striata at 10 and 24 h, respectively, whereas quinolinate injection induced down-regulation between 4 and 6 h after injury. Interestingly, all the excitatory amino acid receptor agonists induced up-regulation of trkB-kinase mRNA levels. This increase was maximal between 2 and 4 h after injection except in kainate injected striata, which showed the peak of expression at 10 h. In contrast, no changes in trkC mRNA expression were observed after striatal excitotoxic injury. In conclusion, our results show that trk receptor mRNA levels are differentially regulated by excitatory amino acid receptor agonists in the striatum, suggesting that changes in the levels of neurotrophin receptors might be involved either in synaptic plasticity processes or in neuronal protection in the striatal excitotoxic paradigm.
在本研究中,我们检测了向纹状体注射谷氨酸受体激动剂后,trkA、trkB和trkC mRNA水平随时间的变化。通过核糖核酸酶保护试验分析了喹啉酸、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)、海人酸或1S,3R-1-氨基环戊烷-1,3-二羧酸(ACPD)诱导的trk mRNA变化。所有高亲和力神经营养因子受体在纹状体内损伤后均表现出不同的调节。在注射海人酸或ACPD的纹状体中,分别在10小时和24小时观察到trkA表达上调,而注射喹啉酸则在损伤后4至6小时诱导下调。有趣的是,所有兴奋性氨基酸受体激动剂均诱导trkB激酶mRNA水平上调。除注射海人酸的纹状体在10小时出现表达峰值外,这种增加在注射后2至4小时最大。相比之下,纹状体兴奋性毒性损伤后未观察到trkC mRNA表达变化。总之,我们的结果表明,trk受体mRNA水平在纹状体中受到兴奋性氨基酸受体激动剂的不同调节,这表明神经营养因子受体水平的变化可能参与了纹状体兴奋性毒性模型中的突触可塑性过程或神经元保护。