De Nicola Alejandro F, Gonzalez Susana L, Labombarda Florencia, González Deniselle Maria Claudia, Garay Laura, Guennoun Rachida, Schumacher Michael
Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental, Buenos Aires, Argentina.
J Mol Neurosci. 2006;28(1):3-15. doi: 10.1385/jmn:28:1:3.
In addition to its traditional role in reproduction, progesterone (PROG) has demonstrated neuroprotective and promyelinating effects in lesions of the peripheral and central nervous systems, including the spinal cord. The latter is a target of PROG, as nuclear receptors, as well as membrane receptors, are expressed by neurons and/or glial cells. When spinal cord injury (SCI) is produced at the thoracic level, several genes become sensitive to PROG in the region caudal to the lesion site. Although the cellular machinery implicated in PROG neuroprotection is only emerging, neurotrophins, their receptors, and signaling cascades might be part of the molecules involved in this process. In rats with SCI, a 3-d course of PROG treatment increased the mRNA of brain-derived neurotrophic factor (BDNF) and BDNF immunoreactivity in perikaryon and processes of motoneurons, whereas chromatolysis was strongly prevented. The increased expression of BDNF correlated with increased immunoreactivity for the BDNF receptor TrkB and for phosphorylated cAMP-responsive element binding in motoneurons. In the same SCI model, PROG restored myelination, according to measurements of myelin basic protein (MBP) and mRNA levels, and further increased the density of NG2+-positive oligodendrocyte progenitors. These cells might be involved in remyelination of the lesioned spinal cord. Interestingly, similarities in the regulation of molecular parameters and some cellular events attributed to PROG and BDNF (i.e., choline acetyltransferase, Na,K-ATPase, MBP, chromatolysis) suggest that BDNF and PROG might share intracellular pathways. Furthermore, PROG-induced BDNF might regulate, in a paracrine or autocrine fashion, the function of neurons and glial cells and prevent the generation of damage.
除了在生殖方面的传统作用外，孕酮（PROG）已在包括脊髓在内的外周和中枢神经系统损伤中表现出神经保护和促进髓鞘形成的作用。脊髓是PROG的作用靶点，因为神经元和/或神经胶质细胞表达核受体以及膜受体。当在胸段产生脊髓损伤（SCI）时，损伤部位尾侧区域的几个基因对PROG变得敏感。尽管参与PROG神经保护的细胞机制刚刚开始显现，但神经营养因子、它们的受体和信号级联反应可能是参与这一过程的分子的一部分。在患有SCI的大鼠中，3天的PROG治疗过程增加了脑源性神经营养因子（BDNF）的mRNA以及运动神经元胞体和突起中的BDNF免疫反应性，同时强烈地防止了染色质溶解。BDNF表达的增加与运动神经元中BDNF受体TrkB以及磷酸化的cAMP反应元件结合蛋白的免疫反应性增加相关。在同一SCI模型中，根据髓鞘碱性蛋白（MBP）和mRNA水平的测量，PROG恢复了髓鞘形成，并进一步增加了NG2 +阳性少突胶质细胞前体细胞的密度。这些细胞可能参与受损脊髓的髓鞘再生。有趣的是，PROG和BDNF在分子参数调节和一些细胞事件方面的相似性（即胆碱乙酰转移酶、钠钾ATP酶、MBP、染色质溶解）表明BDNF和PROG可能共享细胞内途径。此外，PROG诱导的BDNF可能以旁分泌或自分泌方式调节神经元和神经胶质细胞的功能，并防止损伤的产生。
