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Paradoxical effects of apolipoprotein e on cognitive function and clinical progression in mice with experimental autoimmune encephalomyelitis

机译:载脂蛋白e对实验性自身免疫性脑脊髓炎小鼠认知功能和临床进展的悖论作用

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Multiple sclerosis (MS) is an inflammatory demyelinating disease characterized by sensory, motor, and cognitive impairments. Apolipoprotein E (apoE) plays an important role in cholesterol and lipid metabolism in the brain and in susceptibility to cognitive impairment and pathology following brain injury. Studies in mice with a mild form of experimental autoimmune encephalomyelitis (EAE), an MS animal model, support only protective roles for apoE in MS. We examined behavioral and cognitive changes prior to onset of clinical disease and the onset and progression of a more severe form of EAE in female Apoe-/- and C57Bl/6 wild-type mice. Apoe-/- mice had a later day of onset, a later day of peak symptoms and disease severity, and a lower cumulative disease index compared to wild type mice. Apoe-/- mice also showed decreased CD4 + cell invasion following EAE induction compared to wild type mice, and less spinal cord demyelination at 17 but not 30 days following EAE induction. In contrast, EAE-challenged Apoe-/- mice showed reduced exploratory activity, rotorod performance, and impaired contextual fear conditioning compared to wild type animals. These data indicate paradoxical effects of apoE on EAE-induced behavioral and cognitive changes and the onset and progression of clinical disease. ? 2012 Elsevier Inc.
机译:多发性硬化症(MS)是一种以感觉,运动和认知障碍为特征的炎症性脱髓鞘疾病。载脂蛋白E(apoE)在大脑中的胆固醇和脂质代谢以及脑损伤后的认知障碍和病理易感性中起重要作用。在患有轻度形式的实验性自身免疫性脑脊髓炎(EAE)(一种MS动物模型)的小鼠中进行的研究仅支持apoE在MS中的保护作用。我们在雌性Apoe-/-和C57Bl / 6野生型小鼠中检查了临床疾病发作之前行为和认知的变化以及更严重形式的EAE的发作和进展。与野生型小鼠相比,Apoe-/-小鼠的发作较晚,症状和疾病严重程度较晚,且累积疾病指数较低。与野生型小鼠相比,Apoe-/-小鼠在EAE诱导后还显示出CD4 +细胞侵袭减少,并且在EAE诱导后第17天而非30天脊髓脱髓鞘减少。相比之下,与野生型动物相比,EAE挑战的Apoe-/-小鼠显示出降低的探索活动,旋翼机性能和上下文恐惧条件受损。这些数据表明apoE对EAE诱导的行为和认知变化以及临床疾病的发作和进展的反常作用。 ? 2012爱思唯尔公司

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