Brecht S, Buschmann T, Grimm S, Zimmermann M, Herdegen T
II. Institute of Physiology, University of Heidelberg, Germany.
Brain Res Mol Brain Res. 1997 Aug;48(1):7-16. doi: 10.1016/s0169-328x(97)00070-3.
In adult male rats, the expression of the neuropeptide galanin and its co-localization with the c-Jun transcription factor and the NADPH-diaphorase, the marker enzyme for the nitric oxide synthase (NOS), was investigated by immunohistochemistry in axotomized neurons following unilateral stereotaxic transection of the (a) mamillo-thalamic tract, (b) medial forebrain bundle, (c) fimbria fornix bundle and (d) sciatic nerve. This surgical procedure resulted in axotomy of neurons of (a) mamillary ncl. (MnM), (b) substantia nigra compacta (SNC) and paraventricular ncl. of thalamic (PF) neurons, (c) medial septum (MS) and vertical diagonal band of Broca (VDB), and (d) sciatic motoneurons and dorsal root ganglia (DRG). In all of these axotomized neuronal subpopulations, expression of c-Jun appeared between 24 and 36 h post-axotomy and persisted on substantial levels for 15 days in the SNC and for 30-50 days in the MnM, PF, MS, VBD, sciatic DRG and motoneurons. Expression of galanin was seen in axotomized MnM, MS and DRG, but not in SNC, PF and sciatic motoneurons. Galanin-immunoreactivity (IR) appeared between 3 and 5 days after nerve fiber transection and persisted up to 50 days in the MnM, MS and DRGs. The cytoplasmic galanin-IR was almost completely restricted to those neurons showing a nuclear c-Jun expression. Moreover, galanin expression showed a long-lasting co-localization with those neurons that exhibited an increased NADPH-diaphorase reactivity in the MnM and DRG or a residual NADPH-diaphorase reactivity in MS post-axotomy. Very similar to galanin, NADPH-diaphorase was not affected by axotomy in the SNC, PF or sciatic motoneurons. Our findings suggest a common mechanism for galanin and NOS (NADPH-diaphorase activity) expression. Since the galanin promotor contains an AP-1 binding site, c-Jun might trigger the lasting induction of galanin in NOS-positive central neurons that survive the axotomy-evoked injury.
在成年雄性大鼠中，通过免疫组织化学方法研究了神经肽甘丙肽（galanin）的表达及其与c-Jun转录因子和NADPH黄递酶（一氧化氮合酶（NOS）的标记酶）的共定位情况，实验对象为单侧立体定向横断以下神经后的轴突切断神经元：（a）乳头体丘脑束、（b）内侧前脑束、（c）穹窿海马伞束和（d）坐骨神经。该手术导致以下神经元的轴突切断：（a）乳头体核（MnM）、（b）黑质致密部（SNC）和丘脑室旁核（PF）的神经元、（c）内侧隔核（MS）和布罗卡垂直对角带（VDB），以及（d）坐骨运动神经元和背根神经节（DRG）。在所有这些轴突切断的神经元亚群中，c-Jun的表达在轴突切断后24至36小时出现，并在SNC中持续高水平表达15天，在MnM、PF、MS、VBD、坐骨DRG和运动神经元中持续30至50天。甘丙肽的表达在轴突切断的MnM、MS和DRG中可见，但在SNC、PF和坐骨运动神经元中未见。甘丙肽免疫反应性（IR）在神经纤维横断后3至5天出现，并在MnM、MS和DRG中持续长达50天。细胞质中的甘丙肽IR几乎完全局限于那些显示核c-Jun表达的神经元。此外，甘丙肽的表达与那些在MnM和DRG中NADPH黄递酶反应性增加或轴突切断后MS中残留NADPH黄递酶反应性的神经元表现出长期共定位。与甘丙肽非常相似，NADPH黄递酶在SNC、PF或坐骨运动神经元中不受轴突切断的影响。我们的研究结果表明甘丙肽和NOS（NADPH黄递酶活性）表达存在共同机制。由于甘丙肽启动子含有一个AP-1结合位点，c-Jun可能触发在轴突切断引起的损伤中存活的NOS阳性中枢神经元中甘丙肽的持续诱导。
