Novel insights into the mechanisms underlying depression-associated experimental autoimmune encephalomyelitis

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 93; pp. 1 - 10
• Main Authors: Duarte-Silva, Eduardo, Macedo, Danielle, Maes, Michael, Peixoto, Christina Alves
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 13.07.2019
• Subjects: Animal model; Animals; Depression; Depression - etiology; EAE; Encephalomyelitis, Autoimmune, Experimental - complications; Encephalomyelitis, Autoimmune, Experimental - psychology; Mice; MS-associated depression; Multiple Sclerosis - complications; Multiple Sclerosis - psychology; CARS; Animal model; BD; QUINA; CNS; 3-HK; MDD; TNF; IFN; PLP; IDO; EBS; CSF; O&NS; MBP; dpi; GC; MSD; PGE2; PDE5; IL; AD; MOG; MS; FST; TRYCATs; EAE; Depression; MS-associated depression; 3-HAA; SIRS; MAG; TST; ECS; HPA; CIRS
• ISSN: 0278-5846; 1878-4216; 1878-4216
• DOI: 10.1016/j.pnpbp.2019.03.001

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. •Multiple Sclerosis (MS) and EAE are accompanied by depressive symptoms.•Data show depressive symptoms in EAE mice are similar to depression in MS.•Depression in EAE is due to neuroimmunoendocrine changes.•EAE has translational potential and it provides new insights into depression.•EAE can be used to study depression and depression in MS.