Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
Cognitive impairment in an animal model of multiple sclerosis and its amelioration by glatiramer acetate
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DOI：
10.1038/s41598-019-40713-4
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发表时间：
2019-03-11
影响因子：
4.6
通讯作者：
Arnon, Ruth
中科院分区：
文献类型：
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作者：
Aharoni, Rina;Schottlender, Nofar;Arnon, Ruth
在MS动物模型中，实验性自身免疫性脑脊髓炎(EAE)的严重运动障碍阻碍了认知功能的评估。我们开发了一种实验系统，可以评估受EAE影响的小鼠的记忆功能，而无论他们的运动表现如何，从而能够评估疾病持续时间、相关的脑损伤以及格列替拉默醋酸酯(GA)治疗对这些表现的影响。采用延迟非匹配样本(DNMS)T迷宫任务，测试工作记忆和长时记忆。随着临床表现的出现，未经EAE治疗的小鼠的任务表现急剧下降。认知障碍与疾病严重程度相关，未经治疗的EAE小鼠的T迷宫表现与临床症状之间的显著相关性表明。GA处理保留了认知功能，因此尽管它们表现出轻微的运动障碍，但处理的小鼠表现出与幼稚对照组相似的表现。EAE小鼠的认知缺陷与额叶皮质和海马区的炎症和神经退行性损伤相吻合；这些损伤可以通过GA治疗得到缓解。这些综合发现表明，除了运动障碍外，EAE还会导致认知功能的实质性损害，从早期开始，并随着疾病的加重而加重。GA治疗，保存认知能力，防止其与疾病相关的恶化。
The severe motor impairment in the MS animal model experimental autoimmune encephalomyelitis (EAE) obstructs the assessment of cognitive functions. We developed an experimental system that evaluates memory faculties in EAE-affected mice, irrespective of their motor performance, enabling the assessment of cognitive impairments along the disease duration, the associated brain damage, and the consequences of glatiramer acetate (GA) treatment on these manifestations. The delayed-non-matching to sample (DNMS) T-maze task, testing working and long term memory was adapted and utilized. Following the appearance of clinical manifestations task performances of the EAE-untreated mice drastically declined. Cognitive impairments were associated with disease severity, as indicated by a significant correlation between the T-maze performance and the clinical symptoms in EAE-untreated mice. GA-treatment conserved cognitive functions, so that despite their exhibited mild motor impairments, the treated mice performed similarly to naive controls. The cognitive deficit of EAE-mice coincided with inflammatory and neurodegenerative damage to the frontal cortex and the hippocampus; these damages were alleviated by GA-treatment. These combined findings indicate that in addition to motor impairment, EAE leads to substantial impairment of cognitive functions, starting at the early stages and increasing with disease aggravation. GA-treatment, conserves cognitive capacities and prevents its disease related deterioration.