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  - Liu, T.
A1  - McDonnell, PC
A1  - Young, PR
A1  - White, RF
A1  - Sirèn, Anna-Leena
A1  - Hallenbeck, JM
A1  - Barone, FC
A1  - Feuerstein, Giora
T1  - Interleukin-1ß mRNA expression in ischemic rat cortex
N2  - Background and Pur pose: Interleukin-1ß is a proinftammatory cytokine produced by blood-borne and resident brain inftammatory cells. The present study was conducted to determine if interleukin-1ß mRNA was produced in the brain of rats subjected to permanent focal ischemia. Methods: Rat interleukin-1ß cDNA, synthesized from stimulated rat peritoneal macrophage RNA by reverse transcription and polymerase chain reaction and c10ned in plasmid Bluescript KS+, was used to evaluate the expression of interleukin-1ß mRNA in cerebral cortex from spontaneously hypertensive rats and normotensive rats subjected to permanent middle cerebral artery occlusion. Interleukin-1ß mRNA was quantified by Northern blot analysis and compared with rat macrophage RNA standard. To correct for gel loading, blots were also analyzed with cyclophilin cDNA, which encodes an abundant, conserved protein that was unchanged by the experimental conditions. Results: Interleukin-1ß mRNA produced in the ischemic zone was significantly increased from 6 hours to 120 hours, with a maximum of211±24% ofinterleukin-1ß reference standard, ie, 0.2 ng stimulated rat macrophage RNA, mRNA compared with the level in nonischemic cortices (4±2%) at 12 hours after ischemia (P<.OI; n=6). Interleukin-1ß mRNA at 12 hours after ischemia was markedly elevated in hypertensive rats over levels found in two normotensive rat strains. Neurological deficits were also apparent only in the hypertensive rats. Conclusions: Brain interleukin-1ß mRNA is elevated acutely after permanent focal ischemia and especially in hypertensive rats. These data suggest that this potent proinflammatory and procoagulant cytokine might have a role in brain damage following ischemia.
KW  - Gehirn
KW  - Durchblutung
KW  - cerebraI ischemia
KW  - cytokines
KW  - neuronal damage
KW  - rats
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-47442
ER  -