Donnerer J, Liebmann I, Schicho R
Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
Pharmacology. 2005 Feb;73(2):97-101. doi: 10.1159/000081625. Epub 2004 Oct 18.
It was the aim of the present study to investigate by RT-PCR the regulation of the mRNA of the neurosteroid-synthesizing enzyme 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and of the vanilloid receptor TRPV1 in dorsal root ganglia (DRGs) of rats during the process of capsaicin denervation of primary sensory neurons and the following regeneration. The expression of 3beta-HSD in DRG was increased 3 days after the capsaicin treatment, and it remained at that level during a 22 day observation period. The expression of TRPV1, a specific marker of capsaicin-sensitive small sensory neurons connected to C- and Adelta-fibers, was markedly reduced 3 days after the capsaicin treatment. It slowly recovered during the 22 days observation period reaching almost control levels on day 22. When the capsaicin-treated rats received 5 intraplantar injections of nerve growth factor (NGF), the prototypical neurotrophin for capsaicin-sensitive neurons, on day 1, 2, 3, 5 and 6, both the 3beta-HSD and the TRPV1 mRNA had returned to control levels at the time point 8 days after capsaicin. The present results demonstrate that both 3beta-HSD and TRPV1 are markers for neurodegeneration and neuroregeneration in capsaicin-sensitive primary afferent neurons, and that NGF is an effective tool to induce recovery after peripheral nerve injury.
本研究旨在通过逆转录聚合酶链反应(RT-PCR),调查在辣椒素去神经支配初级感觉神经元及随后的再生过程中,大鼠背根神经节(DRG)中神经甾体合成酶3β-羟基类固醇脱氢酶(3β-HSD)和香草酸受体TRPV1的mRNA的调节情况。辣椒素处理后3天,DRG中3β-HSD的表达增加,并且在22天的观察期内保持在该水平。TRPV1是与C纤维和Aδ纤维相连的辣椒素敏感小感觉神经元的特异性标志物,其表达在辣椒素处理后3天显著降低。在22天的观察期内它缓慢恢复,在第22天达到几乎对照水平。当用辣椒素处理的大鼠在第1、2、3、5和6天接受5次足底内注射神经生长因子(NGF)时,NGF是辣椒素敏感神经元的典型神经营养因子,在辣椒素处理后8天的时间点,3β-HSD和TRPV1的mRNA均恢复到对照水平。目前结果表明,3β-HSD和TRPV1都是辣椒素敏感初级传入神经元神经变性和神经再生的标志物,并且NGF是诱导周围神经损伤后恢复的有效工具。