González S L, Labombarda F, González Deniselle M C, Guennoun R, Schumacher M, De Nicola A F
INSERM U488, Hôpital de Bicêtre, 80 rue du Général Leclerc, 94276 Kremlim-Bicêtre, Paris, France.
Neuroscience. 2004;125(3):605-14. doi: 10.1016/j.neuroscience.2004.02.024.
Progesterone (PROG) provides neuroprotection to the injured central and peripheral nervous system. These effects may be due to regulation of myelin synthesis in glial cells and also to direct actions on neuronal function. Recent studies point to neurotrophins as possible mediators of hormone action. Here, we show that the expression of brain-derived neurotrophic factor (BDNF) at both the mRNA and protein levels was increased by PROG treatment in ventral horn motoneurons from rats with spinal cord injury (SCI). Semiquantitative in situ hybridization revealed that SCI reduced BDNF mRNA levels by 50% in spinal motoneurons (control: 53.5+/-7.5 grains/mm(2) vs. SCI: 27.5+/-1.2, P<0.05), while PROG administration to injured rats (4 mg/kg/day during 3 days, s.c.) elicited a three-fold increase in grain density (SCI+PROG: 77.8+/-8.3 grains/mm(2), P<0.001 vs. SCI). In addition, PROG enhanced BDNF immunoreactivity in motoneurons of the lesioned spinal cord. Analysis of the frequency distribution of immunoreactive densities (chi(2): 812.73, P<0.0001) showed that 70% of SCI+PROG motoneurons scored as dark stained whereas only 6% of neurons in the SCI group belonged to this density score category (P<0.001). PROG also prevented the lesion-induced chromatolytic degeneration of spinal cord motoneurons as determined by Nissl staining. In the normal intact spinal cord, PROG significantly increased BDNF inmunoreactivity in ventral horn neurons, without changes in mRNA levels. Our findings suggest that PROG enhancement of endogenous neuronal BDNF could provide a trophic environment within the lesioned spinal cord and might be part of the PROG activated-pathways to provide neuroprotection.
孕酮（PROG）为受损的中枢和外周神经系统提供神经保护。这些作用可能归因于对神经胶质细胞中髓鞘合成的调节，也归因于对神经元功能的直接作用。最近的研究指出神经营养因子可能是激素作用的介质。在此，我们表明脊髓损伤（SCI）大鼠腹角运动神经元经PROG处理后，脑源性神经营养因子（BDNF）的mRNA和蛋白水平表达均增加。半定量原位杂交显示，SCI使脊髓运动神经元中BDNF mRNA水平降低50%（对照：53.5±7.5颗粒/mm² 对SCI：27.5±1.2，P<0.05），而对受伤大鼠皮下注射PROG（4mg/kg/天，共3天）使颗粒密度增加了三倍（SCI+PROG：77.8±8.3颗粒/mm²，与SCI相比P<0.001）。此外，PROG增强了损伤脊髓运动神经元中的BDNF免疫反应性。免疫反应密度频率分布分析（χ²：812.73，P<0.0001）表明，70%的SCI+PROG运动神经元染色较深，而SCI组中只有6%的神经元属于该密度评分类别（P<0.001）。通过尼氏染色确定，PROG还可防止损伤诱导的脊髓运动神经元染色质溶解变性。在正常完整脊髓中，PROG显著增加腹角神经元中的BDNF免疫反应性，而mRNA水平无变化。我们的数据表明，PROG增强内源性神经元BDNF可能在损伤脊髓内提供一个营养环境，并且可能是PROG激活的提供神经保护的信号通路的一部分。
