Widenfalk J, Widmer H R, Spenger C
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Neuroreport. 1999 May 14;10(7):1433-9. doi: 10.1097/00001756-199905140-00009.
The identification of endogenous neurotrophic factors and their receptors in human spinal cord is important not only to understand development, but also in the consideration of possible future therapies for neurodegenerative disorders and trauma. Using in situ hybridization, the expression of glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN), persephin (PSP), GFRalpha-1, GFRalpha-2, GFRalpha-3 and RET mRNA in human fetal spinal cord was studied. Strong GDNF mRNA hybridization signal, presumably restricted to Clarke's nucleus, was detected in the thoracic spinal cord. mRNA encoding GFRalpha-1 was expressed in the entire spinal cord gray matter with particularly high expression in the ventral horn. GFRbeta-1 was also expressed more weakly in dorsal root ganglia. NTN and persephin mRNA were not detected in either the fetal spinal cord or the dorsal root ganglia. mRNA coding for GFRalpha-2, however, was found in most cells of the spinal cord gray matter. A strong expression of GFRalpha-3 mRNA was detected in dorsal root ganglia cells and Schwann cells. The transducing receptor RET was expressed strongly in motorneurons and dorsal root ganglion neurons. We conclude that basic features concerning the role of the GDNF family of ligands and their receptors revealed in rodents applies to humans.
鉴定人类脊髓中的内源性神经营养因子及其受体不仅对于理解脊髓发育很重要，而且在考虑未来针对神经退行性疾病和创伤的可能治疗方法时也很重要。利用原位杂交技术，研究了胶质细胞源性神经营养因子（GDNF）、神经营养素（NTN）、帕西芬（PSP）、GFRα-1、GFRα-2、GFRα-3和RET mRNA在人类胎儿脊髓中的表达。在胸段脊髓中检测到强烈的GDNF mRNA杂交信号，推测该信号局限于克拉克核。编码GFRα-1的mRNA在整个脊髓灰质中均有表达，在腹角中表达尤为高。GFRβ-1在背根神经节中的表达也较弱。在胎儿脊髓或背根神经节中均未检测到NTN和帕西芬mRNA。然而，在脊髓灰质的大多数细胞中发现了编码GFRα-2的mRNA。在背根神经节细胞和施万细胞中检测到GFRα-3 mRNA的强烈表达。转导受体RET在运动神经元和背根神经节神经元中强烈表达。我们得出结论，在啮齿动物中揭示的关于GDNF配体家族及其受体作用的基本特征适用于人类。
