Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS

Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain conten...

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Published in:Journal of neuroinflammation 2015-12, Vol.12 (232), p.234-234, Article 234
Main Authors: Schrewe, L, Lill, C M, Liu, T, Salmen, A, Gerdes, L A, Guillot-Noel, L, Akkad, D A, Blaschke, P, Graetz, C, Hoffjan, S, Kroner, A, Demir, S, Böhme, A, Rieckmann, P, ElAli, A, Hagemann, N, Hermann, D M, Cournu-Rebeix, I, Zipp, F, Kümpfel, T, Buttmann, M, Zettl, U K, Fontaine, B, Bertram, L, Gold, R, Chan, A
Format: Article
Language:English
Subjects:
Analysis
Animals
Apolipoproteins
Apolipoproteins E - genetics
Apolipoproteins E - immunology
Biochemistry, Molecular Biology
Care and treatment
Complications and side effects
Encephalomyelitis, Autoimmune, Experimental - genetics
Encephalomyelitis, Autoimmune, Experimental - pathology
Female
Fluorescent Antibody Technique
Genotype
Humans
Life Sciences
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Multiple sclerosis
Multiple Sclerosis - genetics
Real-Time Polymerase Chain Reaction
Sex Factors
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Summary:Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. MOG(35-55) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. EAE disease course was slightly attenuated in male apoE-deficient (apoE (-/-) ) mice compared to wildtype mice (cumulative median score: apoE (-/-)  = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE (-/-) mice compared to wildtype mice (cumulative median score: apoE (-/-)  = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; p 
ISSN:1742-2094
1742-2094
DOI:10.1186/s12974-015-0429-y