Marco Sònia, Canudas Anna M, Canals Josep M, Gavaldà Núria, Pérez-Navarro Esther, Alberch Jordi
Departament de Biologia Cel small middle dotlular i Anatomia Patològica, Facultat de Medicina, IDIBAPS, Universitat de Barcelona, Casanova 143, Barcelona, E-08036, Spain.
Exp Neurol. 2002 Apr;174(2):243-52. doi: 10.1006/exnr.2001.7859.
Glial cell line-derived neurotrophic factor (GDNF) family ligands are important regulators of neuronal development and maintenance of the connectivity in the basal ganglia and show neuroprotective activities in several paradigms of brain injury. The mRNAs of two members of this family, GDNF and neurturin, and also their receptors have been detected in the basal ganglia. In the present work, we analyzed the time course changes in the expression of these neurotrophic factors and receptors in the adult rat striatum, induced by quinolinate or kainate excitotoxicity. Our results show that stimulation of NMDA or non-NMDA receptors induced different effects on the mRNA levels analyzed. Expression of GDNF and its preferred receptor, GDNF family receptor-alpha1 (GFRalpha1), was transiently up-regulated by quinolinate and kainate, but with differing intensity and temporal pattern. Immunohistochemical analysis showed that, although GDNF and GFRalpha1 were initially localized in neurons, excitotoxicity induced the expression of these proteins in astrocyte-like cells. Neurturin mRNA levels were only up-regulated after quinolinate injection, whereas quinolinate or kainate injection did not modify GFRalpha2 mRNA. The mRNA for the common receptor, c-Ret, was up-regulated by both agonists with similar temporal pattern but with differing intensity. Immunohistochemical analysis showed that c-Ret protein was located on neurons. These changes in mRNA levels and protein localization of GDNF family components could reflect an endogenous trophic response of striatal cells to different excitotoxic insults.
胶质细胞源性神经营养因子（GDNF）家族配体是神经元发育和基底神经节中连接性维持的重要调节因子，并在几种脑损伤模型中显示出神经保护活性。该家族的两个成员GDNF和神经营养因子-3的mRNA及其受体已在基底神经节中被检测到。在本研究中，我们分析了喹啉酸或海藻酸兴奋性毒性诱导成年大鼠纹状体中这些神经营养因子及其受体表达的时间进程变化。我们的结果表明，NMDA或非NMDA受体的刺激对所分析的mRNA水平产生了不同的影响。GDNF及其首选受体GDNF家族受体-α1（GFRα1）的表达被喹啉酸和海藻酸短暂上调，但强度和时间模式不同。免疫组织化学分析表明，尽管GDNF和GFRα1最初定位于神经元，但兴奋性毒性诱导这些蛋白在星形胶质样细胞中表达。神经营养因子-3的mRNA水平仅在注射喹啉酸后上调，而注射喹啉酸或海藻酸并未改变GFRα2的mRNA水平。共同受体c-Ret的mRNA被两种激动剂上调，时间模式相似但强度不同。免疫组织化学分析表明，c-Ret蛋白位于神经元上。GDNF家族成分的mRNA水平和蛋白定位的这些变化可能反映了纹状体细胞对不同兴奋性毒性损伤的内源性营养反应。
