Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), Recife, PE, Brazil; Postgraduate Program in Biosciences and Biotechnology for Health (PPGBBS), Oswaldo Cruz Foundation (FIOCRUZ-PE)/Aggeu Magalhães Institute (IAM), Recife, PE, Brazil.
Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, CE, Brazil; Department of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jul 13;93:1-10. doi: 10.1016/j.pnpbp.2019.03.001. Epub 2019 Mar 5.
Multiple Sclerosis (MS) is a chronic autoimmune disease characterized by neuroinflammation, demyelination and neuroaxonal degeneration affecting >2 million people around the world. MS is often accompanied by psychiatric comorbidities such as major depressive disorder (MDD), which presents a lifetime prevalence of around 50% in MS patients. Experimental Autoimmune Encephalomyelitis (EAE) is an animal model extensively used to study MS. EAE mimics the autoimmune nature of MS, as well as its inflammatory and demyelinating mechanisms also presenting predictive validity. There are important similarities between EAE and MS-associated depression (MSD). The mechanisms shared by these disorders include peripheral inflammation, neuroinflammation, mitochondrial dysfunctions, oxidative stress, nitrosative stress, lowered antioxidant defenses, increased bacterial translocation into the systemic circulation, and microglial pathology. Although the role of the immune-inflammatory system in MDD has been established in the 1990's, only few studies addressed immune pathways as a major determinant of depressive-like behavior in EAE. Therefore, in the present study we aimed at revising the current literature on EAE as an animal model to investigate the comorbidity between MS and MDD. In this regard, we revised the current literature on behavioral alterations in EAE, the possible mechanisms involved in this comorbidity and the potential and limitations of using this animal model to study depressive-like behavior.
多发性硬化症（MS）是一种慢性自身免疫性疾病，其特征为神经炎症、脱髓鞘和神经轴突变性，影响全球超过 200 万人。MS 常伴有精神共病，如重度抑郁症（MDD），在 MS 患者中终生患病率约为 50%。实验性自身免疫性脑脊髓炎（EAE）是一种广泛用于研究 MS 的动物模型。EAE 模拟了 MS 的自身免疫性质，以及其炎症和脱髓鞘机制，也具有预测有效性。EAE 和与 MS 相关的抑郁症（MSD）之间存在重要的相似性。这些疾病共同的机制包括外周炎症、神经炎症、线粒体功能障碍、氧化应激、亚硝化应激、抗氧化防御降低、细菌向全身循环易位增加以及小胶质细胞病理学。尽管免疫炎症系统在 MDD 中的作用在 20 世纪 90 年代已经确立，但只有少数研究探讨了免疫途径作为 EAE 中抑郁样行为的主要决定因素。因此，在本研究中，我们旨在回顾 EAE 作为一种动物模型来研究 MS 和 MDD 共病的相关文献。在这方面，我们回顾了 EAE 中行为改变的现有文献、这种共病涉及的可能机制，以及使用这种动物模型研究抑郁样行为的潜力和局限性。
