Bruns Marla B, Miller Michael W
Department of Neuroscience and Physiology, State University of New York-Upstate Medical University, Syracuse, New York 13210, USA.
J Neurochem. 2007 Mar;100(5):1155-68. doi: 10.1111/j.1471-4159.2006.04301.x.
The hypothesis tested is that cortical neurotrophins communicate through an inducible autocrine/paracrine mechanism. As ethanol (Et) can induce cortical nerve growth factor (NGF) expression, adult rats were challenged with Et on three consecutive days per week for 6 weeks. The focus of the study was layer V, the chief repository of receptor-expressing neuronal cell bodies. Brains were collected immediately after the sixth Et exposure or 72 h later [i.e., following withdrawal (WD)]. Double-label in situ hybridization-immunohistochemistry studies showed that many neuronal somata co-expressed NGF mRNA with NGF, trkA, or phosphorylated trk (p-trk), essential components of an inducible autocrine system. The frequencies of co-labeling were affected by neither Et nor WD. On the contrary, Et increased the number of NGF mRNA-expressing neurons and the amount of NGF mRNA expressed per cell. Et also increased total cortical concentration of NGF protein, the number of layer V neurons expressing trkA transcript, the amount of trkA mRNA expressed per neuron, and trkA phosphorylation. Following WD, the frequency of NGF-mRNA-expressing cells increased, although transcript and protein content fell. WD induced an increase in trkA mRNA and protein expression, however, p-trk expression was unaffected. Thus, Et treatment reveals that layer V has inducible autocrine/paracrine and anterograde neurotrophin systems. WD unveils the dynamism and recruitability of these systems.
所检验的假设是皮质神经营养因子通过一种可诱导的自分泌/旁分泌机制进行通信。由于乙醇（Et）可诱导皮质神经生长因子（NGF）表达，成年大鼠每周连续三天接受Et处理，共6周。研究重点是V层，即表达受体的神经元细胞体的主要储存部位。在第六次Et暴露后或72小时后（即戒断后）立即收集大脑。双重标记原位杂交 - 免疫组织化学研究表明，许多神经元胞体与NGF、trkA或磷酸化trk（p-trk）共同表达NGF mRNA，trkA和p-trk是可诱导自分泌系统的重要组成部分。共标记频率不受Et或戒断的影响。相反，Et增加了表达NGF mRNA的神经元数量以及每个细胞表达的NGF mRNA量。Et还增加了皮质中NGF蛋白的总浓度、表达trkA转录本的V层神经元数量、每个神经元表达的trkA mRNA量以及trkA磷酸化水平。戒断后，表达NGF - mRNA的细胞频率增加，尽管转录本和蛋白质含量下降。戒断诱导trkA mRNA和蛋白质表达增加，然而，p-trk表达不受影响。因此，Et处理表明V层具有可诱导的自分泌/旁分泌和顺行性神经营养因子系统。戒断揭示了这些系统的动态性和可募集性。
