Differential expression of sonic hedgehog immunoreactivity during lesion evolution in autoimmune encephalomyelitis
Differential expression of sonic hedgehog immunoreactivity during lesion evolution in autoimmune encephalomyelitis
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DOI：
10.1093/jnen/64.5.404
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发表时间：
2005-05-01
影响因子：
3.2
通讯作者：
Storch, MK
中科院分区：
文献类型：
--
作者：
Seifert, T;Bauer, J;Storch, MK
信号分子Sonic hedgehog（Shh）参与中枢神经系统发育的几个过程。最近的报道表明，Shh表达在成人大脑的某些病理条件下也起作用，包括多发性硬化症及其动物模型。然而，Shh信号在免疫介导的脱髓鞘疾病中的作用仍然不确定。本研究的目的是探讨髓鞘-少突胶质细胞-糖蛋白诱导的实验性自身免疫性脑脊髓炎（MOG-EAE）（一种强烈模仿多发性硬化的模型）病变演变过程中Shh免疫反应性（Shh-IR）的分布模式。DA大鼠主动诱发MOG-EAE。主动免疫后20 - 120天，在石蜡包埋的中枢神经系统切片上用光学和共聚焦显微镜进行组织学评价。Shh-IR在MOG-EAE病变演变的所有阶段均存在于病变内。最高染色强度的Shh被发现在髓鞘再生病变。在主动脱髓鞘，非活动性脱髓鞘病变，并在髓鞘再生病变，Shh-IR检测到巨噬细胞，内皮细胞和星形胶质细胞。Shh-IR在轴突中仅存在于髓鞘再生病变中。虽然Shh信号通路在实验性自身免疫性脑脊髓炎中的确切分子机制尚未确定，但我们的研究结果可能暗示Shh信号通路在促进髓鞘再生中的作用。
The signaling molecule Sonic hedgehog (Shh) is involved in several processes of central nervous system development. Recent reports indicate that Shh expression plays a role also in certain pathologic conditions in the adult brain, including multiple sclerosis and its animal model. However, the role of Shh signaling in immune-mediated demyelinating disease remains still uncertain. The aim of our study was to investigate the distribution pattern of Shh immunoreactivity (Shh-IR) during lesion evolution in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE), a model strongly mimicking multiple sclerosis. MOG-EAE was actively induced in DA rats. Histologic evaluation was performed with light and confocal microscopy on paraffin-embedded central nervous system sections from days 20 to 120 after active immunization. Shh-IR was present within the lesions of MOG-EAE during all stages of lesion evolution. The highest staining intensity for Shh was found in remyelinating lesions. In actively demyelinating, inactive demyelinated lesions, and in remyelinating lesions, Shh-IR was detected in macrophages, endothelium, and astrocytes. Shh-IR in axons was exclusively present in remyelinating lesions. Although the exact molecular mechanisms of the Shh-signaling pathway in experimental autoimmune encephalomyelitis are yet to be determined, our findings may imply a role of Shh signaling in facilitating remyelination.