Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
J Neuroinflammation. 2013 Apr 22;10:49. doi: 10.1186/1742-2094-10-49.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by entry of activated T cells and antigen presenting cells into the central nervous system and subsequent autoimmune destruction of nerve myelin. Previous studies revealed that non-selective inhibition of poly(ADP-ribose) polymerases (PARPs) 1 and 2 protect against neuroinflammation and motor dysfunction associated with EAE, but the role of the PARP-2 isoform has not yet been investigated selectively.
EAE was induced in mice lacking PARP-2, and neurological EAE signs, blood-spine barrier (BSB) permeability, demyelination and inflammatory infiltration were monitored for 35 days after immunization. Mice lacking PARP-2 exhibited significantly reduced overall disease burden and peak neurological dysfunction. PARP-2 deletion also significantly delayed EAE onset and reduced BSB permeability, demyelination and central nervous system (CNS) markers of proinflammatory Th1 and Th17 T helper lymphocytes.
This study represents the first description of a significant role for PARP-2 in neuroinflammation and neurological dysfunction in EAE.
实验性自身免疫性脑脊髓炎（EAE）是多发性硬化症的动物模型，其特征是激活的 T 细胞和抗原呈递细胞进入中枢神经系统，随后发生神经髓鞘的自身免疫性破坏。先前的研究表明，非选择性抑制多聚（ADP-核糖）聚合酶（PARPs）1 和 2 可预防与 EAE 相关的神经炎症和运动功能障碍，但 PARP-2 同工型的作用尚未得到选择性研究。
在缺乏 PARP-2 的小鼠中诱导 EAE，并在免疫后 35 天监测神经 EAE 体征、血脊屏障（BSB）通透性、脱髓鞘和炎症浸润。缺乏 PARP-2 的小鼠表现出明显减轻的整体疾病负担和峰值神经功能障碍。PARP-2 缺失还显著延迟了 EAE 的发作，并降低了 BSB 的通透性、脱髓鞘以及中枢神经系统（CNS）中促炎 Th1 和 Th17 T 辅助淋巴细胞的标志物。
本研究首次描述了 PARP-2 在 EAE 中的神经炎症和神经功能障碍中的重要作用。
