Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune neurological disease and is the most common subtype of MS. In addition, it is associated with the development of depression and anxiety. To date, depressive- and anxiety-like behaviours were only studied using models of progressive MS, which causes severe motor alterations. Thus, we sought to standardise the depressive and anxiety-like behaviours in an RRMS model induced by experimental autoimmune encephalomyelitis (RR-EAE) in mice. The RR-EAE model was induced in C57BL/6 female mice using myelin oligodendrocyte glycoprotein (MOG35-55) antigen and Quillaja saponin (Quil A) as an adjuvant. The immunisation of RR-EAE did not induce locomotor alteration but caused relapsing-remitting induction of clinical scores in mice until 35 post-immunization (p.i.). Also, increased levels of tumour necrosis factor alpha (TNF-α), astrocyte marker (GFAP), and microglial markers (IBA-1) were detected in the prefrontal cortex at 35 p.i. of RR-EAE. In the open field test, RR-EAE mice showed decreased time spent at the centre and sniffing behaviour (at days 21 and 34 p.i.). Also, on day 35 p.i. the RR-EAE group spent less time in the open arms and had decreased open-arm entries compared to control mice in the elevated plus maze (EPM) test, confirming the anxiety-like behaviour. At day 36° p.i. in the tail suspension test, mice showed depression-like behaviour with decreased latency time and increased immobility time. Thus, the RR-EAE model mimics the neuroinflammatory and behavioural features of the RRMS, including depression- and anxiety-like symptoms.

复发缓解型多发性硬化症 (RRMS) 是一种自身免疫性神经系统疾病，也是 MS 最常见的亚型。此外，它还与抑郁和焦虑的发展有关。迄今为止，抑郁和焦虑样行为仅使用进行性多发性硬化症模型进行研究，这种模型会导致严重的运动改变。因此，我们试图标准化小鼠实验性自身免疫性脑脊髓炎 (RR-EAE) 诱导的 RRMS 模型中的抑郁和焦虑样行为。使用髓磷脂少突胶质细胞糖蛋白（MOG35-55）抗原和皂树皂苷（Quil A）作为佐剂在C57BL/6雌性小鼠中诱导RR-EAE模型。RR-EAE 的免疫不会诱导小鼠运动改变，但会导致小鼠临床评分的复发缓解直至免疫后 35 小时 (pi)。此外，在 RR-EAE 35 pi 时，在前额皮质中检测到肿瘤坏死因子 α (TNF-α)、星形胶质细胞标记物 (GFAP )和小胶质细胞标记物 (IBA-1)水平升高。在旷场测试中，RR-EAE 小鼠表现出在中心停留的时间和嗅探行为减少（接种后第 21 天和第 34 天）。此外，在感染后第 35 天，在高架十字迷宫 (EPM) 测试中，与对照组小鼠相比，RR-EAE 组在张开臂中花费的时间更少，并且张开臂进入的次数也减少，这证实了类似焦虑的行为。在尾部悬吊试验中，感染后第 36° 天，小鼠表现出抑郁样行为，潜伏时间缩短，不动时间增加。因此，RR-EAE 模型模拟了 RRMS 的神经炎症和行为特征，包括抑郁和焦虑样症状。