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J Neuroinflammation. 2015 Dec 16;12:234. doi: 10.1186/s12974-015-0429-y.

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

Author information

1
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, Bochum, 44791, Germany. lisa.schrewe@rub.de.
2
Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany. lill@molgen.mpg.de.
3
Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. lill@molgen.mpg.de.
4
Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. lill@molgen.mpg.de.
5
Max Planck Institute for Human Development, Berlin, Germany. tianliu@mpib-berlin.mpg.de.
6
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, Bochum, 44791, Germany. anke.salmen@rub.de.
7
Institute for Clinical Neuroimmunology, Medical Campus Grosshadern, Ludwig Maximilian University, Munich, Germany. LisaAnn.Gerdes@med.uni-muenchen.de.
8
Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France. lena.guillot-noel@upmc.fr.
9
Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany. Amer.Akkad@rub.de.
10
Department of Neurology, University of Rostock, Rostock, Germany. paul.blaschke@uni-rostock.de.
11
Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Christiane.Graetz@unimedizin-mainz.de.
12
Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany. Sabine.Hoffjan@rub.de.
13
Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada. antje.kroner@gmail.com.
14
Department of Neurology, University of Würzburg, Würzburg, Germany. antje.kroner@gmail.com.
15
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, Bochum, 44791, Germany. seray.demir@rub.de.
16
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, Bochum, 44791, Germany. anne.boehme@rub.de.
17
Department of Neurology, University of Würzburg, Würzburg, Germany. peter.rieckmann@sozialstiftung-bamberg.de.
18
Neuroscience Axis, Research Center of CHU de Québec-CHUL, Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Québec City, QC, Canada. ayman.el-ali@crchuq.ulaval.ca.
19
Department of Vascular Neurology and Dementia, University of Duisburg-Essen, Essen, Germany. ayman.el-ali@crchuq.ulaval.ca.
20
Department of Vascular Neurology and Dementia, University of Duisburg-Essen, Essen, Germany. Nina.Hagemann@uk-essen.de.
21
Department of Vascular Neurology and Dementia, University of Duisburg-Essen, Essen, Germany. Dirk.Hermann@uk-essen.de.
22
Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France. isabelle.rebeix@upmc.fr.
23
Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. frauke.zipp@unimedizin-mainz.de.
24
Institute for Clinical Neuroimmunology, Medical Campus Grosshadern, Ludwig Maximilian University, Munich, Germany. Tania.Kuempfel@med.uni-muenchen.de.
25
Department of Neurology, University of Würzburg, Würzburg, Germany. m.buttmann@uni-wuerzburg.de.
26
Department of Neurology, University of Rostock, Rostock, Germany. uwe.zettl@med.uni-rostock.de.
27
Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013, Paris, France. bertrand.fontaine@upmc.fr.
28
AP-HP, Hôpital de la Pitié Salpêtrière, Département des maladies du système nerveux, F-75013, Paris, France. bertrand.fontaine@upmc.fr.
29
Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany. lbertram@molgen.mpg.de.
30
Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. lbertram@molgen.mpg.de.
31
School of Public Health, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK. lbertram@molgen.mpg.de.
32
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, Bochum, 44791, Germany. ralf.gold@rub.de.
33
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, Bochum, 44791, Germany. Andrew.chan@rub.de.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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 < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex.

CONCLUSIONS:

apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.

PMID:
26669675
PMCID:
PMC4681148
DOI:
10.1186/s12974-015-0429-y
[Indexed for MEDLINE]
Free PMC Article

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