Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
Brain Res. 2010 Apr 22;1326:1-14. doi: 10.1016/j.brainres.2010.02.049. Epub 2010 Feb 20.
A disintegrin and metalloproteinase (ADAM) 12 represents a member of a large family of similarly structured multi-domain proteins. In the central nervous system (CNS), ADAM12 has been suggested to play a role in brain development, glioblastoma cell proliferation, and in experimental autoimmune encephalomyelitis. Furthermore, ADAM12 was reported to be almost exclusively expressed by oligodendrocytes and could, therefore, be considered as suitable marker for this cell type. In the present study, we investigated ADAM12 expression in the healthy and pathologically altered murine CNS. As pathological paradigm, we used the cuprizone demyelination model in which myelin loss during multiple sclerosis is imitated. Besides APC(+) oligodendrocytes, SMI311(+) neurons and GFAP(+) astrocytes express ADAM12 in the adult mouse brain. ADAM12 expression was further analyzed in vitro. After the induction of demyelination, we observed that activated astrocytes are the main source of ADAM12 in brain regions affected by oligodendrocyte loss. Exposure of astrocytes in vitro to either lipopolysaccharides (LPS), tumor necrosis factor alpha (TNFalpha), glutamate, or hydrogen peroxide revealed a highly stimulus-specific regulation of ADAM12 expression which was not seen in microglial BV2 cells. It appears that LPS- and TNFalpha-induced ADAM12 expression is mediated via the classic NFkappaB pathway. In summary, we demonstrated that ADAM12 is not a suitable marker for oligodendrocytes. Our results further suggest that ADAM12 might be implicated in the course of distinct CNS diseases such as demyelinating disorders.
解整合素金属蛋白酶 12（ADAM12）是结构相似的多功能蛋白家族中的一个成员。在中枢神经系统（CNS）中，ADAM12 被认为在脑发育、神经胶质瘤细胞增殖和实验性自身免疫性脑脊髓炎中发挥作用。此外，ADAM12 几乎只在少突胶质细胞中表达，因此可以被认为是该细胞类型的合适标志物。在本研究中，我们研究了 ADAM12 在健康和病理改变的小鼠中枢神经系统中的表达。作为病理范例，我们使用了 cuprizone 脱髓鞘模型，该模型模拟了多发性硬化症中的髓鞘丢失。除了 APC（+）少突胶质细胞外，SMI311（+）神经元和 GFAP（+）星形胶质细胞在成年小鼠大脑中表达 ADAM12。进一步分析了 ADAM12 的体外表达。在脱髓鞘诱导后，我们观察到激活的星形胶质细胞是受少突胶质细胞丢失影响的脑区中 ADAM12 的主要来源。体外暴露于脂多糖（LPS）、肿瘤坏死因子-α（TNFα）、谷氨酸或过氧化氢的星形胶质细胞显示出 ADAM12 表达的高度刺激特异性调节，而在小胶质细胞 BV2 细胞中未观察到这种调节。似乎 LPS 和 TNFα 诱导的 ADAM12 表达是通过经典的 NFkappaB 途径介导的。总之，我们证明 ADAM12 不是少突胶质细胞的合适标志物。我们的结果进一步表明，ADAM12 可能参与了脱髓鞘疾病等不同中枢神经系统疾病的发生。
