Motor neuron pathology in experimental autoimmune encephalomyelitis:: studies in THY1-YFP transgenic mice
Motor neuron pathology in experimental autoimmune encephalomyelitis:: studies in THY1-YFP transgenic mice
复制标题
DOI：
10.1093/brain/awh550
复制
发表时间：
2005-08-01
期刊：
影响因子：
14.5
通讯作者：
Pleasure, D
中科院分区：
文献类型：
--
作者：
Bannerman, PG;Hahn, A;Pleasure, D
以运动神经元中表达黄色荧光蛋白转基因的成年雄性C57BL/6小鼠为实验对象，用完全弗氏佐剂（CFA）中的髓鞘少突胶质细胞糖蛋白肽35-55 （MOG肽）免疫诱导实验性自身免疫性脑脊髓炎（EAE）。同一转基因菌株的对照小鼠给予不含MOG肽的CFA。在发病早期，EAE小鼠出现腰骶脊髓炎症、脱髓鞘和轴突断裂。在服用mog肽14周后，这些异常变得不那么突出，但小鼠仍然虚弱，并且与进行性多发性硬化症患者一样，脊髓萎缩已经发展。MOG肽- eae小鼠腰椎脊髓运动神经元未见明显损失。然而，在病程早期，运动神经元树突被破坏，运动神经元低磷酸化神经丝- h （hypp - nf - h）免疫反应性表达减弱。mog肽后14周，hypp - nf - h表达恢复正常，但运动神经元树突异常持续存在，运动神经元核周萎缩出现。我们假设这些运动神经元异常导致了这种EAE形式的虚弱，并推测在进行性多发性硬化症患者中也存在类似的运动神经元异常。
Using adult male C57BL/6 mice that express a yellow fluorescent protein transgene in their motor neurons, we induced experimental autoimmune encephalomyelitis (EAE) by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) in complete Freund's adjuvant (CFA). Control mice of the same transgenic strain received CFA without MOG peptide. Early in the course of their illness, the EAE mice showed lumbosacral spinal cord inflammation, demyelination and axonal fragmentation. By 14 weeks post-MOG peptide, these abnormalities were much less prominent, but the mice remained weak and, as in patients with progressive multiple sclerosis, spinal cord atrophy had developed. There was no significant loss of lumbar spinal cord motor neurons in the MOG peptide-EAE mice. However, early in the course of the illness, motor neuron dendrites were disrupted and motor neuron expression of hypophosphorylated neurofilament-H (hypoP-NF-H) immunoreactivity was diminished. By 14 weeks post-MOG peptide, hypoP-NF-H expression had returned to normal, but motor neuron dendritic abnormalities persisted and motor neuron perikaryal atrophy had appeared. We hypothesize that these motor neuron abnormalities contribute to weakness in this form of EAE and speculate that similar motor neuron abnormalities are present in patients with progressive multiple sclerosis.