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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 |
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| creator | 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 |
| description | 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 |
| doi_str_mv | 10.1186/s12974-015-0429-y |
| format | article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4681148</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A451670499</galeid><sourcerecordid>A451670499</sourcerecordid><originalsourceid>FETCH-LOGICAL-c528t-90fd7aec43eea725c2669436b56c5c2d003e314e256d0178fae4c91e54345e1d3</originalsourceid><addsrcrecordid>eNptUk1v1DAUtBCIfsAP4IIicaGHFD_HH_EFaVUttNIiDoWz5TrPW1dZO8TZFfvvcbSltBXywfbzzHje6BHyDug5QCs_ZWBa8ZqCqClnut6_IMegOKsZ1fzlo_MROcn5jtKGCclekyMmpdRSiWNyfRV3mKewtlNIsUq-yvi7zgO64IOr0Ht0U57rdkh9GNIwpglDrJZVgWfc4Rim_fy-XCwrG7vq2_Ub8srbPuPb-_2U_Pyy_HFxWa--f726WKxqJ1g71Zr6Tll0vEG0iglXXGneyBshXbl0xS42wLF47iio1lvkTgMK3nCB0DWn5PNBd9jebLBzGKfR9mYYw8aOe5NsME9fYrg167QzXLYAvC0CZweB22e0y8XKzDUKTFDWwg4K9uP9Z2P6tS2RmU3IDvveRkzbbErWWmvJeFOgH55B79J2jCWKglJaQquk-oda2x5NiD4Vj24WNQsuQCpaBAvq_D-osjrcBJci-lDqTwhwILgx5Tyif2gMqJmnxhympvQmzDw1Zl847x8H-cD4OybNH-5wuug</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1779618767</pqid></control><display><type>article</type><title>Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS</title><source>Publicly Available Content Database</source><source>PubMed Central</source><creator>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</creator><creatorcontrib>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</creatorcontrib><description>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 < 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.
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.</description><identifier>ISSN: 1742-2094</identifier><identifier>EISSN: 1742-2094</identifier><identifier>DOI: 10.1186/s12974-015-0429-y</identifier><identifier>PMID: 26669675</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>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</subject><ispartof>Journal of neuroinflammation, 2015-12, Vol.12 (232), p.234-234, Article 234</ispartof><rights>COPYRIGHT 2015 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2015</rights><rights>Attribution</rights><rights>Schrewe et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-90fd7aec43eea725c2669436b56c5c2d003e314e256d0178fae4c91e54345e1d3</citedby><cites>FETCH-LOGICAL-c528t-90fd7aec43eea725c2669436b56c5c2d003e314e256d0178fae4c91e54345e1d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681148/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1779618767?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,25783,27957,27958,37047,37048,44625,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26669675$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-01250281$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Schrewe, L</creatorcontrib><creatorcontrib>Lill, C M</creatorcontrib><creatorcontrib>Liu, T</creatorcontrib><creatorcontrib>Salmen, A</creatorcontrib><creatorcontrib>Gerdes, L A</creatorcontrib><creatorcontrib>Guillot-Noel, L</creatorcontrib><creatorcontrib>Akkad, D A</creatorcontrib><creatorcontrib>Blaschke, P</creatorcontrib><creatorcontrib>Graetz, C</creatorcontrib><creatorcontrib>Hoffjan, S</creatorcontrib><creatorcontrib>Kroner, A</creatorcontrib><creatorcontrib>Demir, S</creatorcontrib><creatorcontrib>Böhme, A</creatorcontrib><creatorcontrib>Rieckmann, P</creatorcontrib><creatorcontrib>ElAli, A</creatorcontrib><creatorcontrib>Hagemann, N</creatorcontrib><creatorcontrib>Hermann, D M</creatorcontrib><creatorcontrib>Cournu-Rebeix, I</creatorcontrib><creatorcontrib>Zipp, F</creatorcontrib><creatorcontrib>Kümpfel, T</creatorcontrib><creatorcontrib>Buttmann, M</creatorcontrib><creatorcontrib>Zettl, U K</creatorcontrib><creatorcontrib>Fontaine, B</creatorcontrib><creatorcontrib>Bertram, L</creatorcontrib><creatorcontrib>Gold, R</creatorcontrib><creatorcontrib>Chan, A</creatorcontrib><title>Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS</title><title>Journal of neuroinflammation</title><addtitle>J Neuroinflammation</addtitle><description>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 < 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.
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.</description><subject>Analysis</subject><subject>Animals</subject><subject>Apolipoproteins</subject><subject>Apolipoproteins E - genetics</subject><subject>Apolipoproteins E - immunology</subject><subject>Biochemistry, Molecular Biology</subject><subject>Care and treatment</subject><subject>Complications and side effects</subject><subject>Encephalomyelitis, Autoimmune, Experimental - genetics</subject><subject>Encephalomyelitis, Autoimmune, Experimental - pathology</subject><subject>Female</subject><subject>Fluorescent Antibody Technique</subject><subject>Genotype</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - genetics</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Sex Factors</subject><issn>1742-2094</issn><issn>1742-2094</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNptUk1v1DAUtBCIfsAP4IIicaGHFD_HH_EFaVUttNIiDoWz5TrPW1dZO8TZFfvvcbSltBXywfbzzHje6BHyDug5QCs_ZWBa8ZqCqClnut6_IMegOKsZ1fzlo_MROcn5jtKGCclekyMmpdRSiWNyfRV3mKewtlNIsUq-yvi7zgO64IOr0Ht0U57rdkh9GNIwpglDrJZVgWfc4Rim_fy-XCwrG7vq2_Ub8srbPuPb-_2U_Pyy_HFxWa--f726WKxqJ1g71Zr6Tll0vEG0iglXXGneyBshXbl0xS42wLF47iio1lvkTgMK3nCB0DWn5PNBd9jebLBzGKfR9mYYw8aOe5NsME9fYrg167QzXLYAvC0CZweB22e0y8XKzDUKTFDWwg4K9uP9Z2P6tS2RmU3IDvveRkzbbErWWmvJeFOgH55B79J2jCWKglJaQquk-oda2x5NiD4Vj24WNQsuQCpaBAvq_D-osjrcBJci-lDqTwhwILgx5Tyif2gMqJmnxhympvQmzDw1Zl847x8H-cD4OybNH-5wuug</recordid><startdate>20151216</startdate><enddate>20151216</enddate><creator>Schrewe, L</creator><creator>Lill, C M</creator><creator>Liu, T</creator><creator>Salmen, A</creator><creator>Gerdes, L A</creator><creator>Guillot-Noel, L</creator><creator>Akkad, D A</creator><creator>Blaschke, P</creator><creator>Graetz, C</creator><creator>Hoffjan, S</creator><creator>Kroner, A</creator><creator>Demir, S</creator><creator>Böhme, A</creator><creator>Rieckmann, P</creator><creator>ElAli, A</creator><creator>Hagemann, N</creator><creator>Hermann, D M</creator><creator>Cournu-Rebeix, I</creator><creator>Zipp, F</creator><creator>Kümpfel, T</creator><creator>Buttmann, M</creator><creator>Zettl, U K</creator><creator>Fontaine, B</creator><creator>Bertram, L</creator><creator>Gold, R</creator><creator>Chan, A</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope></search><sort><creationdate>20151216</creationdate><title>Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-90fd7aec43eea725c2669436b56c5c2d003e314e256d0178fae4c91e54345e1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Apolipoproteins</topic><topic>Apolipoproteins E - genetics</topic><topic>Apolipoproteins E - immunology</topic><topic>Biochemistry, Molecular Biology</topic><topic>Care and treatment</topic><topic>Complications and side effects</topic><topic>Encephalomyelitis, Autoimmune, Experimental - genetics</topic><topic>Encephalomyelitis, Autoimmune, Experimental - pathology</topic><topic>Female</topic><topic>Fluorescent Antibody Technique</topic><topic>Genotype</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - genetics</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Sex Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schrewe, L</creatorcontrib><creatorcontrib>Lill, C M</creatorcontrib><creatorcontrib>Liu, T</creatorcontrib><creatorcontrib>Salmen, A</creatorcontrib><creatorcontrib>Gerdes, L A</creatorcontrib><creatorcontrib>Guillot-Noel, L</creatorcontrib><creatorcontrib>Akkad, D A</creatorcontrib><creatorcontrib>Blaschke, P</creatorcontrib><creatorcontrib>Graetz, C</creatorcontrib><creatorcontrib>Hoffjan, S</creatorcontrib><creatorcontrib>Kroner, A</creatorcontrib><creatorcontrib>Demir, S</creatorcontrib><creatorcontrib>Böhme, A</creatorcontrib><creatorcontrib>Rieckmann, P</creatorcontrib><creatorcontrib>ElAli, A</creatorcontrib><creatorcontrib>Hagemann, N</creatorcontrib><creatorcontrib>Hermann, D M</creatorcontrib><creatorcontrib>Cournu-Rebeix, I</creatorcontrib><creatorcontrib>Zipp, F</creatorcontrib><creatorcontrib>Kümpfel, T</creatorcontrib><creatorcontrib>Buttmann, M</creatorcontrib><creatorcontrib>Zettl, U K</creatorcontrib><creatorcontrib>Fontaine, B</creatorcontrib><creatorcontrib>Bertram, L</creatorcontrib><creatorcontrib>Gold, R</creatorcontrib><creatorcontrib>Chan, A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of neuroinflammation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schrewe, L</au><au>Lill, C M</au><au>Liu, T</au><au>Salmen, A</au><au>Gerdes, L A</au><au>Guillot-Noel, L</au><au>Akkad, D A</au><au>Blaschke, P</au><au>Graetz, C</au><au>Hoffjan, S</au><au>Kroner, A</au><au>Demir, S</au><au>Böhme, A</au><au>Rieckmann, P</au><au>ElAli, A</au><au>Hagemann, N</au><au>Hermann, D M</au><au>Cournu-Rebeix, I</au><au>Zipp, F</au><au>Kümpfel, T</au><au>Buttmann, M</au><au>Zettl, U K</au><au>Fontaine, B</au><au>Bertram, L</au><au>Gold, R</au><au>Chan, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS</atitle><jtitle>Journal of neuroinflammation</jtitle><addtitle>J Neuroinflammation</addtitle><date>2015-12-16</date><risdate>2015</risdate><volume>12</volume><issue>232</issue><spage>234</spage><epage>234</epage><pages>234-234</pages><artnum>234</artnum><issn>1742-2094</issn><eissn>1742-2094</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>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 < 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.
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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>26669675</pmid><doi>10.1186/s12974-015-0429-y</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of neuroinflammation, 2015-12, Vol.12 (232), p.234-234, Article 234 |
| issn | 1742-2094 1742-2094 |
| language | eng |
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| 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 |
| title | Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T19%3A32%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Investigation%20of%20sex-specific%20effects%20of%20apolipoprotein%20E%20on%20severity%20of%20EAE%20and%20MS&rft.jtitle=Journal%20of%20neuroinflammation&rft.au=Schrewe,%20L&rft.date=2015-12-16&rft.volume=12&rft.issue=232&rft.spage=234&rft.epage=234&rft.pages=234-234&rft.artnum=234&rft.issn=1742-2094&rft.eissn=1742-2094&rft_id=info:doi/10.1186/s12974-015-0429-y&rft_dat=%3Cgale_pubme%3EA451670499%3C/gale_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c528t-90fd7aec43eea725c2669436b56c5c2d003e314e256d0178fae4c91e54345e1d3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1779618767&rft_id=info:pmid/26669675&rft_galeid=A451670499&rfr_iscdi=true |