Tikhomirova M S, Karpenko M N, Kirik O V, Sukhorukova E G, Korzhevskiĭ D É, Klimenko V M
Ross Fiziol Zh Im I M Sechenova. 2015 Jan;101(1):74-84.
The regenerative capacity of the Central Nervous System (CNS) is a key factor implicated in the pathogenesis of neurodegenerative diseases. In the present study, the regenerative capacity of the CNS is considered using one of the markers of regeneration, Growth Associated Protein-43 (GAP-43) and its proteolytic fragment GAP-43-3 in the Experimental Autoimmune Encephalomyelitis (EAE) animal model of multiple sclerosis. The EAE on Wistar rats was characterized as an adequate model of multiple sclerosis, with typical clinical (pares and paralysis) and morphological (infiltration of spinal cord and deformation of motoneurons) disorders. Normally about 60% of GAP-43 is cleaved by m-calpain and stays in the form of GAP-43-3. During severe form of EAE up to 85% of GAP-43 can be found cleaved. We speculated that the cleavage of GAP-43 can play a crucial role for regenerative capacity of CNS during EAE development. Thus the distribution of GAP-43 and GAP-43-3 in the spinal cord was analyzed. The manifestation of clinical signs of EAE has been found to be in correlation with the levels of GAP-43 proteolysis both in the homogenate of the spinal cord and on the spinal cord slices. The immunoreactive staining enabled the observation of the accumulation of GAP-43-3 predominantly in microglial cells.
中枢神经系统(CNS)的再生能力是与神经退行性疾病发病机制相关的关键因素。在本研究中,利用再生标志物之一生长相关蛋白43(GAP-43)及其蛋白水解片段GAP-43-3,在多发性硬化症的实验性自身免疫性脑脊髓炎(EAE)动物模型中研究中枢神经系统的再生能力。以Wistar大鼠的EAE作为多发性硬化症的合适模型,其具有典型的临床症状(轻瘫和瘫痪)和形态学改变(脊髓浸润和运动神经元变形)。正常情况下,约60%的GAP-43被m-钙蛋白酶切割,以GAP-43-3的形式存在。在严重的EAE形式中,高达85%的GAP-43可被发现已被切割。我们推测,在EAE发展过程中,GAP-43的切割可能对中枢神经系统的再生能力起关键作用。因此,分析了GAP-43和GAP-43-3在脊髓中的分布。已发现EAE临床症状的表现与脊髓匀浆和脊髓切片中GAP-43蛋白水解水平相关。免疫反应性染色能够观察到GAP-43-3主要在小胶质细胞中积累。