Dept. Neurology and Sagol Neuroscience Center, Sheba Medical Center, Tel-Hashomer, Israel; Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Affiliated to Sackler Medical School, Tel Aviv University, Israel.
J Autoimmun. 2013 Sep;45:24-30. doi: 10.1016/j.jaut.2013.06.010. Epub 2013 Jul 5.
Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy (a sudden weakening of posture muscle tone usually triggered by emotion) caused by the loss of orexin neurons in the hypothalamus. Autoimmune mechanisms are implicated in narcolepsy by increased frequency of specific HLA alleles and the presence of specific autoantibody (anti-Tribbles homolog 2 (TRIB2) antibodies) in the sera of patients with narcolepsy. Presently, we passively transferred narcolepsy to naïve mice by injecting intra-cerebra-ventricularly (ICV) pooled IgG positive for anti-TRIB2 antibodies. Narcolepsy-IgG-injected mice had a loss of the NeuN (neuronal marker), synaptophysin (synaptic marker) and orexin-positive neurons in the lateral hypothalamus area in narcolepsy compared to control-IgG-injected mice and these changes were associated with narcolepsy-like immobility attacks at four weeks post injection and with hyperactivity and long term memory deficits in the staircase and novel object recognition tests. Similar behavioral and cognitive deficits are observed in narcoleptic patients. This is the first report of passive transfer of experimental narcolepsy to naïve mice induced by autoantibodies and supports the autoimmune pathogenesis in narcolepsy.
发作性睡病是一种睡眠障碍，其特征是白天过度嗜睡和猝倒（一种姿势肌肉张力突然减弱的现象，通常由情绪引发），这是由于下丘脑的食欲素神经元丧失引起的。自身免疫机制通过增加特定 HLA 等位基因的频率和发作性睡病患者血清中特定自身抗体（抗 Tribbles 同源物 2（TRIB2）抗体）的存在而与发作性睡病有关。目前，我们通过向内侧脑室（ICV）注射抗 TRIB2 抗体阳性的 IgG 来被动地将发作性睡病转移到幼稚小鼠。与对照 IgG 注射小鼠相比，发作性睡病 IgG 注射小鼠的外侧下丘脑区域的 NeuN（神经元标记物）、突触小泡蛋白（突触标记物）和食欲素阳性神经元丢失，这些变化与注射后四周出现类似发作性睡病的不动攻击以及在楼梯和新物体识别测试中出现过度活跃和长期记忆缺陷有关。在发作性睡病患者中也观察到类似的行为和认知缺陷。这是首次报道通过自身抗体将实验性发作性睡病被动转移到幼稚小鼠，支持了发作性睡病的自身免疫发病机制。
