Jongen J L M, Haasdijk E D, Sabel-Goedknegt H, van der Burg J, Vecht Ch J, Holstege J C
Department of Neuroscience, Erasmus MC-University Medical Center Rotterdam, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
Exp Neurol. 2005 Jul;194(1):255-66. doi: 10.1016/j.expneurol.2005.02.019.
Glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) are potent trophic factors for dorsal root ganglion cells. In addition, these factors are produced in subsets of dorsal root ganglion cells and transported anterogradely to their terminals in the superficial dorsal horn of the spinal cord, where they constitute the only source of GDNF and BDNF. We investigated the effect of 10 mug GDNF and BDNF injected by lumbar puncture on the expression of the immediate early gene (IEG) products c-Fos, c-Jun, and Krox-24 in the adult rat dorsal horn. In the dorsal horn of S1 spinal segments, GDNF and BDNF induced a strong increase in IEG expression, which was most pronounced in laminae I and II (2.9- to 4.5-fold). More distal from the injection site, in the dorsal horn of L1/L2 spinal segments, the increase in IEG expression was less pronounced, suggesting a concentration-dependent effect. In order to explain the effects of intrathecally injected GDNF, we investigated whether lumbo-sacral dorsal horn neurons expressed RET protein, the signal-transducing element of the receptor complex for GDNF. It was found that several of these neurons contained RET immunoreactivity and that some of the RET-labeled neurons had the appearance of nociceptive-specific cells, confirming their presumed role in pain transmission. Additionally, using double-labeling immunofluorescence combined with confocal microscopy, it was found that after intrathecal GDNF injection 35% of c-Fos-labeled cells were also labeled for RET. These results demonstrate that intrathecally administered GDNF and BDNF induce IEG expression in dorsal horn neurons in the adult rat, supposedly by way of their cognate receptors, which are present on these neurons. We further suggest that the endogenous release of GDNF and BDNF, triggered by nociceptive stimuli, is involved in the induction of changes in spinal nociceptive transmission as in various pain states.
胶质细胞系源性神经营养因子（GDNF）和脑源性神经营养因子（BDNF）是对背根神经节细胞有强大作用的营养因子。此外，这些因子在背根神经节细胞的亚群中产生，并顺行运输至脊髓背角浅层的终末，在那里它们构成了GDNF和BDNF的唯一来源。我们研究了通过腰椎穿刺注射10微克GDNF和BDNF对成年大鼠背角中即早基因（IEG）产物c-Fos、c-Jun和Krox-24表达的影响。在S1脊髓节段的背角中，GDNF和BDNF诱导IEG表达强烈增加，在I层和II层最为明显（2.9至4.5倍）。在离注射部位更远的L1/L2脊髓节段的背角中，IEG表达的增加不太明显，提示存在浓度依赖性效应。为了解释鞘内注射GDNF的作用，我们研究了腰骶部背角神经元是否表达RET蛋白，RET蛋白是GDNF受体复合物的信号转导元件。发现其中一些神经元含有RET免疫反应性，并且一些RET标记的神经元具有伤害性特异性细胞的外观，证实了它们在疼痛传递中的假定作用。此外，使用双标记免疫荧光结合共聚焦显微镜发现，鞘内注射GDNF后，35%的c-Fos标记细胞也被标记为RET。这些结果表明，鞘内给予GDNF和BDNF可诱导成年大鼠背角神经元中的IEG表达，推测是通过这些神经元上存在的同源受体实现的。我们进一步认为，由伤害性刺激触发的GDNF和BDNF的内源性释放参与了各种疼痛状态下脊髓伤害性传递变化的诱导过程。
