TY  - JOUR
A1  - Schrewe, L.
A1  - Lill, C. M.
A1  - Liu, T.
A1  - Salmen, A.
A1  - Gerdes, L. A.
A1  - Guillot-Noel, L.
A1  - Akkad, D. A.
A1  - Blaschke, P.
A1  - Graetz, C.
A1  - Hoffjan, S.
A1  - Kroner, A.
A1  - Demir, S.
A1  - Böhme, A.
A1  - Rieckmann, P.
A1  - El Ali, A.
A1  - Hagemann, N.
A1  - Hermann, D. M.
A1  - Cournu-Rebeix, I.
A1  - Zipp, F.
A1  - Kümpfel, T.
A1  - Buttmann, M.
A1  - Zettl, U. K.
A1  - Fontaine, B.
A1  - Bertram, L.
A1  - Gold, R.
A1  - Chan, A.
T1  - Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS
JF  - Journal of Neuroinflammation
N2  - 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 naive 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.
KW  - immune
KW  - apoE
KW  - gender
KW  - inflammation
KW  - association studies in genetics
KW  - apoe
KW  - CNS disease
KW  - system
KW  - multiple sclerosis
KW  - MSSS
KW  - experimental autoimmune encephalomyelitis
KW  - disease severity
KW  - cognitive function
KW  - Alzheimer disease
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136252
VL  - 12
IS  - 234
ER  - 
TY  - JOUR
A1  - Blachutzik, Jörg O.
A1  - Demir, Faith
A1  - Kreuzer, Ines
A1  - Hedrich, Rainer
A1  - Harms, Gregory S.
T1  - Methods of staining and visualization of sphingolipid enriched and non-enriched plasma membrane regions of Arabidopsis thaliana with fluorescent dyes and lipid analogues
N2  - Background: Sterols and Sphingolipids form lipid clusters in the plasma membranes of cell types throughout the animal and plant kingdoms. These lipid domains provide a medium for protein signaling complexes at the plasma membrane and are also observed to be principal regions of membrane contact at the inception of infection. We visualized different specific fluorescent lipophilic stains of the both sphingolipid enriched and non-sphingolipid enriched regions in the plasma membranes of live protoplasts of Arabidopsis thaliana. Results: Lipid staining protocols for several fluorescent lipid analogues in plants are presented. The most emphasis was placed on successful protocols for the single and dual staining of sphingolipid enriched regions and exclusion of sphingolipid enriched regions on the plasma membrane of Arabidopsis thaliana protoplasts. A secondary focus was placed to ensure that these staining protocols presented still maintain cell viability. Furthermore, the protocols were successfully tested with the spectrally sensitive dye Laurdan. Conclusion: Almost all existing staining procedures of the plasma membrane with fluorescent lipid analogues are specified for animal cells and tissues. In order to develop lipid staining protocols for plants, procedures were established with critical steps for the plasma membrane staining of Arabidopsis leaf tissue and protoplasts. The success of the plasma membrane staining protocols was additionally verified by measurements of lipid dynamics by the fluorescence recovery after photobleaching technique and by the observation of new phenomena such as time dependent lipid polarization events in living protoplasts, for which a putative physiological relevance is suggested.
KW  - Arabidopsis thaliana
KW  - Protoplasts
KW  - Lipid polarization
KW  - Lipophilic fluorescent dyes
KW  - Laurdan
KW  - Sphingolipid
KW  - Liquid (dis-) ordered phase
KW  - Plasma membrane
KW  - Fluorescence mi
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75433
ER  -