Hippocampal damage in mouse and human forms of systemic autoimmune disease
Hippocampal damage in mouse and human forms of systemic autoimmune disease
复制标题
DOI：
10.1002/hipo.10205
复制
发表时间：
2004-01-01
期刊：
影响因子：
3.5
通讯作者：
Sakic, B
中科院分区：
文献类型：
--
作者：
Ballok, DA;Woulfe, J;Sakic, B
系统性红斑狼疮（SLE）常伴有神经精神（NP）和病因不明的认知功能障碍。通过使用自身免疫性MRL-Ipr小鼠作为NP-SLE的动物模型，我们研究了自身免疫性、海马损伤和行为功能障碍之间的关系。荧光玉石B（FI B）染色和抗泛素（抗UB）免疫细胞化学用于评估年轻（无症状）和老年（患病）小鼠的神经元损伤，而自发交替行为（SA B）用于估计海马功能障碍的严重程度。通过长期服用免疫抑制药物环磷酰胺（CY）来检测自身免疫和神经病理学之间的因果关系。与同类MRL +/+对照相比，SAB获得率和“逆转”试验中的表现在患病的MRL-Ipr小鼠中受损，表明空间学习策略的使用有限。FJB阳性神经元和抗Ub颗粒在CA 3区常见。相反，CY治疗减弱了SAB缺陷和总体FIB染色。与小鼠大脑相似，死于NP-SLE的患者的海马体显示CA 3区和齿状回的神经元密度降低，以及这些区域的FIB阳性增加。在灰质中观察到胶质增生和神经元丢失，脉络丛中常见T淋巴细胞和间质钙化。总之，这些结果表明，全身性自身免疫诱导显着的海马损伤，这可能是NP-SLE的情感和认知缺陷的基础。(C)2004 Wiley-Liss，Inc.
Systemic lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric (NP) and cognitive deficits of unknown etiology. By using autoimmune MRL-Ipr mice as an animal model of NP-SLE, we examine the relationship between autoimmunity, hippocampal damage, and behavioral dysfunction. Fluoro jade B (FIB) staining and anti-ubiquitin (anti-Ub) immunocytochemistry were used to assess neuronal damage in young (asymptomatic) and aged (diseased) mice, while spontaneous alternation behavior (SAB) was used to estimate the severity of hippocampal dysfunction. The causal relationship between autoimmunity and neuropathology was tested by prolonged administration of the immunosuppressive drug cyclophosphamide (CY). In comparison to congenic MRL +/+ controls, SAB acquisition rates and performance in the "reversal" trial were impaired in diseased MRL-Ipr mice, suggesting limited use of the spatial learning strategy. FJB-positive neurons and anti-Ub particles were frequent in the CA3 region. Conversely, CY treatment attenuated the SAB deficit and overall FIB staining. Similarly to mouse brain, the hippocampus from a patient who died from NP-SLE showed reduced neuronal density in the CA3 region and dentate gyrus, as well as increased FIB positivity in these regions. Gliosis and neuronal loss were observed in the gray matter, and T lymphocytes and stromal calcifications were common in the choroid plexus. Taken together, these results suggest that systemic autoimmunity induces significant hippocampal damage, which may underlie affective and cognitive deficits in NP-SLE. (C) 2004 Wiley-Liss, Inc.