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中枢神经系统雪旺细胞在体外表现出少突胶质前体细胞样钾通道激活和抗原表达。

CNS Schwann cells display oligodendrocyte precursor-like potassium channel activation and antigenic expression in vitro.

机构信息

Department of Pathology, University of Veterinary Medicine, Bünteweg 17, 30559, Hannover, Germany.

出版信息

J Neural Transm (Vienna). 2014 Jun;121(6):569-81. doi: 10.1007/s00702-014-1163-9. Epub 2014 Feb 1.

Abstract

Central nervous system (CNS) injury triggers production of myelinating Schwann cells from endogenous oligodendrocyte precursors (OLPs). These CNS Schwann cells may be attractive candidates for novel therapeutic strategies aiming to promote endogenous CNS repair. However, CNS Schwann cells have been so far mainly characterized in situ regarding morphology and marker expression, and it has remained enigmatic whether they display functional properties distinct from peripheral nervous system (PNS) Schwann cells. Potassium channels (K+) have been implicated in progenitor and glial cell proliferation after injury and may, therefore, represent a suitable pharmacological target. In the present study, we focused on the function and expression of voltage-gated K+ channels Kv(1-12) and accessory β-subunits in purified adult canine CNS and PNS Schwann cell cultures using electrophysiology and microarray analysis and characterized their antigenic phenotype. We show here that K+ channels differed significantly in both cell types. While CNS Schwann cells displayed prominent K D-mediated K+ currents, PNS Schwann cells elicited K(D-) and K(A-type) K+ currents. Inhibition of K+ currents by TEA and Ba2+ was more effective in CNS Schwann cells. These functional differences were not paralleled by differential mRNA expression of Kv(1-12) and accessory β-subunits. However, O4/A2B5 and GFAP expressions were significantly higher and lower, respectively, in CNS than in PNS Schwann cells. Taken together, this is the first evidence that CNS Schwann cells display specific properties not shared by their peripheral counterpart. Both Kv currents and increased O4/A2B5 expression were reminiscent of OLPs suggesting that CNS Schwann cells retain OLP features during maturation.

摘要

中枢神经系统(CNS)损伤会触发内源性少突胶质前体细胞(OLP)产生髓鞘形成雪旺细胞。这些中枢神经系统雪旺细胞可能是有吸引力的候选者,适用于旨在促进内源性中枢神经系统修复的新的治疗策略。然而,迄今为止,中枢神经系统雪旺细胞主要在形态和标记物表达方面在原位进行了表征,它们是否表现出与周围神经系统(PNS)雪旺细胞不同的功能特性仍然是一个谜。钾通道(K+)已被牵涉到损伤后的祖细胞和神经胶质细胞增殖中,因此,可能是一个合适的药物靶点。在本研究中,我们使用电生理学和微阵列分析,重点研究了纯化的成年犬中枢神经系统和周围神经系统雪旺细胞培养物中电压门控 K+通道 Kv(1-12)和辅助β亚基的功能和表达,并对其抗原表型进行了表征。我们在这里表明,K+通道在这两种细胞类型中差异显著。虽然中枢神经系统雪旺细胞显示出明显的 K D 介导的 K+电流,但周围神经系统雪旺细胞产生 K(D-)和 K(A- 型) K+电流。K+电流的抑制通过 TEA 和 Ba2+在中枢神经系统雪旺细胞中更有效。这些功能差异与 Kv(1-12)和辅助β亚基的差异 mRNA 表达没有平行关系。然而,O4/A2B5 和 GFAP 的表达在中枢神经系统中分别显著更高和更低,与周围神经系统相比。总之,这是第一个证明中枢神经系统雪旺细胞具有与其周围对应物不同的特定特性的证据。Kv 电流和 O4/A2B5 表达的增加都让人联想到 OLP,这表明中枢神经系统雪旺细胞在成熟过程中保留了 OLP 特征。

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