Sex difference in flux of 27‐hydroxycholesterol into the brain
Background and Purpose The cerebrospinal fluid (CSF)/plasma albumin ratio (QAlb) is believed to reflect the integrity of the blood–brain barrier (BBB). Recently, we reported that QAlb is lower in females. This may be important for uptake of neurotoxic 27‐hydroxycholesterol (27OH) by the brain in par...
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| Veröffentlicht in: | British journal of pharmacology 2021-08, Vol.178 (16), p.3194-3204 |
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| creator | Parrado‐Fernandez, Cristina Leoni, Valerio Saeed, Ahmed Rodriguez‐Rodriguez, Patricia Sandebring‐Matton, Anna Córdoba‐Beldad, Carmen M. Bueno, Paula Gali, Chaitanya Chakravarthi Panzenboeck, Ute Cedazo‐Minguez, Angel Björkhem, Ingemar |
| description | Background and Purpose
The cerebrospinal fluid (CSF)/plasma albumin ratio (QAlb) is believed to reflect the integrity of the blood–brain barrier (BBB). Recently, we reported that QAlb is lower in females. This may be important for uptake of neurotoxic 27‐hydroxycholesterol (27OH) by the brain in particular because plasma levels of 27OH are higher in males. We studied sex differences in the relation between CSF and plasma levels of 27OH and its major metabolite 7α‐hydroxy‐3‐oxo‐4‐cholestenoic acid (7HOCA) with QAlb. We tested the possibility of sex differences in the brain metabolism of 27OH and if its flux into the brain disrupted integrity of the BBB.
Experimental Approach
We have examined our earlier studies looking for sex differences in CSF levels of oxysterols and their relation to QAlb. We utilized an in vitro model for the BBB with primary cultured brain endothelial cells to test if 27OH has a disruptive effect on this barrier. We measured mRNA and protein levels of CYP7B1 in autopsy brain samples.
Key Results
The correlation between CSF levels of 27OH and QAlb was higher in males whereas, with 7HOCA, the correlation was higher in females. No significant sex difference in the expression of CYP7B1 mRNA in brain autopsy samples. A correlation was found between plasma levels of 27OH and QAlb. No support was obtained for the hypothesis that plasma levels of 27OH have a disruptive effect on the BBB.
Conclusions and Implications
The sex differences are discussed in relation to negative effects of 27OH on different brain functions.
LINKED ARTICLES
This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc |
| doi_str_mv | 10.1111/bph.15353 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_465703</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2556222966</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5313-337fc83c70033e89456e7970b6336a8c54f11f26ee955dd30e768063b2759cd43</originalsourceid><addsrcrecordid>eNp1kc9u1DAQxi0EosvCgRdAkThxSGt7Mv5zQUAFFKkSSMDZSpwxSUnjxdmlu7c-Qp-RJ8GQbaGH-mJr5vd9Y83H2FPBD0U-R82qOxQICPfYQlRalQhG3GcLzrkuhTDmgD2apjPOc1PjQ3YAABVKiwv26jNti7YPgRKNnop-LMKw2RYxFFL_urzqdm2K253v4kDTmlIcMrKOxbqjokl1Pz5mD0I9TPRkfy_Z13dvvxyflKcf3384fn1aegQBJYAO3oDXnAOQsRUq0lbzRgGo2nisghBBKiKL2LbASSvDFTRSo_VtBUtWzr7TBa02jVul_rxOOxfr3u1L3_OLXKVQ5xlLZu_kVym2_0TXQlGhASMlz9qXszYD59R6GtepHm5b3OqMfee-xZ_OAFphMRs83xuk-GOTF-fO4iaNeT9OIioppVUqUy9myqc4TYnCzQTB3Z9gXQ7W_Q02s8_-_9INeZ1kBo5m4KIfaHe3k3vz6WS2_A1rya4m</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2556222966</pqid></control><display><type>article</type><title>Sex difference in flux of 27‐hydroxycholesterol into the brain</title><source>Wiley Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SWEPUB Freely available online</source><source>Wiley Free Content</source><source>Alma/SFX Local Collection</source><creator>Parrado‐Fernandez, Cristina ; Leoni, Valerio ; Saeed, Ahmed ; Rodriguez‐Rodriguez, Patricia ; Sandebring‐Matton, Anna ; Córdoba‐Beldad, Carmen M. ; Bueno, Paula ; Gali, Chaitanya Chakravarthi ; Panzenboeck, Ute ; Cedazo‐Minguez, Angel ; Björkhem, Ingemar</creator><creatorcontrib>Parrado‐Fernandez, Cristina ; Leoni, Valerio ; Saeed, Ahmed ; Rodriguez‐Rodriguez, Patricia ; Sandebring‐Matton, Anna ; Córdoba‐Beldad, Carmen M. ; Bueno, Paula ; Gali, Chaitanya Chakravarthi ; Panzenboeck, Ute ; Cedazo‐Minguez, Angel ; Björkhem, Ingemar</creatorcontrib><description>Background and Purpose
The cerebrospinal fluid (CSF)/plasma albumin ratio (QAlb) is believed to reflect the integrity of the blood–brain barrier (BBB). Recently, we reported that QAlb is lower in females. This may be important for uptake of neurotoxic 27‐hydroxycholesterol (27OH) by the brain in particular because plasma levels of 27OH are higher in males. We studied sex differences in the relation between CSF and plasma levels of 27OH and its major metabolite 7α‐hydroxy‐3‐oxo‐4‐cholestenoic acid (7HOCA) with QAlb. We tested the possibility of sex differences in the brain metabolism of 27OH and if its flux into the brain disrupted integrity of the BBB.
Experimental Approach
We have examined our earlier studies looking for sex differences in CSF levels of oxysterols and their relation to QAlb. We utilized an in vitro model for the BBB with primary cultured brain endothelial cells to test if 27OH has a disruptive effect on this barrier. We measured mRNA and protein levels of CYP7B1 in autopsy brain samples.
Key Results
The correlation between CSF levels of 27OH and QAlb was higher in males whereas, with 7HOCA, the correlation was higher in females. No significant sex difference in the expression of CYP7B1 mRNA in brain autopsy samples. A correlation was found between plasma levels of 27OH and QAlb. No support was obtained for the hypothesis that plasma levels of 27OH have a disruptive effect on the BBB.
Conclusions and Implications
The sex differences are discussed in relation to negative effects of 27OH on different brain functions.
LINKED ARTICLES
This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc</description><identifier>ISSN: 0007-1188</identifier><identifier>ISSN: 1476-5381</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/bph.15353</identifier><identifier>PMID: 33345295</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>27‐hydroxycholesterol ; Autopsy ; Blood-brain barrier ; Cerebrospinal fluid ; CYP7B1 ; Endothelial cells ; Gender differences ; Gene expression ; Medicin och hälsovetenskap ; mRNA ; neurodegeneration ; Neurotoxicity ; Oxysterols, Lifelong Health and Therapeutics–Research Papers ; Plasma ; Plasma levels ; Research Paper ; Sex ; Sex differences</subject><ispartof>British journal of pharmacology, 2021-08, Vol.178 (16), p.3194-3204</ispartof><rights>2020 The Authors. published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.</rights><rights>2020 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5313-337fc83c70033e89456e7970b6336a8c54f11f26ee955dd30e768063b2759cd43</citedby><cites>FETCH-LOGICAL-c5313-337fc83c70033e89456e7970b6336a8c54f11f26ee955dd30e768063b2759cd43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbph.15353$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbph.15353$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,552,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33345295$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:145838220$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Parrado‐Fernandez, Cristina</creatorcontrib><creatorcontrib>Leoni, Valerio</creatorcontrib><creatorcontrib>Saeed, Ahmed</creatorcontrib><creatorcontrib>Rodriguez‐Rodriguez, Patricia</creatorcontrib><creatorcontrib>Sandebring‐Matton, Anna</creatorcontrib><creatorcontrib>Córdoba‐Beldad, Carmen M.</creatorcontrib><creatorcontrib>Bueno, Paula</creatorcontrib><creatorcontrib>Gali, Chaitanya Chakravarthi</creatorcontrib><creatorcontrib>Panzenboeck, Ute</creatorcontrib><creatorcontrib>Cedazo‐Minguez, Angel</creatorcontrib><creatorcontrib>Björkhem, Ingemar</creatorcontrib><title>Sex difference in flux of 27‐hydroxycholesterol into the brain</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Background and Purpose
The cerebrospinal fluid (CSF)/plasma albumin ratio (QAlb) is believed to reflect the integrity of the blood–brain barrier (BBB). Recently, we reported that QAlb is lower in females. This may be important for uptake of neurotoxic 27‐hydroxycholesterol (27OH) by the brain in particular because plasma levels of 27OH are higher in males. We studied sex differences in the relation between CSF and plasma levels of 27OH and its major metabolite 7α‐hydroxy‐3‐oxo‐4‐cholestenoic acid (7HOCA) with QAlb. We tested the possibility of sex differences in the brain metabolism of 27OH and if its flux into the brain disrupted integrity of the BBB.
Experimental Approach
We have examined our earlier studies looking for sex differences in CSF levels of oxysterols and their relation to QAlb. We utilized an in vitro model for the BBB with primary cultured brain endothelial cells to test if 27OH has a disruptive effect on this barrier. We measured mRNA and protein levels of CYP7B1 in autopsy brain samples.
Key Results
The correlation between CSF levels of 27OH and QAlb was higher in males whereas, with 7HOCA, the correlation was higher in females. No significant sex difference in the expression of CYP7B1 mRNA in brain autopsy samples. A correlation was found between plasma levels of 27OH and QAlb. No support was obtained for the hypothesis that plasma levels of 27OH have a disruptive effect on the BBB.
Conclusions and Implications
The sex differences are discussed in relation to negative effects of 27OH on different brain functions.
LINKED ARTICLES
This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc</description><subject>27‐hydroxycholesterol</subject><subject>Autopsy</subject><subject>Blood-brain barrier</subject><subject>Cerebrospinal fluid</subject><subject>CYP7B1</subject><subject>Endothelial cells</subject><subject>Gender differences</subject><subject>Gene expression</subject><subject>Medicin och hälsovetenskap</subject><subject>mRNA</subject><subject>neurodegeneration</subject><subject>Neurotoxicity</subject><subject>Oxysterols, Lifelong Health and Therapeutics–Research Papers</subject><subject>Plasma</subject><subject>Plasma levels</subject><subject>Research Paper</subject><subject>Sex</subject><subject>Sex differences</subject><issn>0007-1188</issn><issn>1476-5381</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>D8T</sourceid><recordid>eNp1kc9u1DAQxi0EosvCgRdAkThxSGt7Mv5zQUAFFKkSSMDZSpwxSUnjxdmlu7c-Qp-RJ8GQbaGH-mJr5vd9Y83H2FPBD0U-R82qOxQICPfYQlRalQhG3GcLzrkuhTDmgD2apjPOc1PjQ3YAABVKiwv26jNti7YPgRKNnop-LMKw2RYxFFL_urzqdm2K253v4kDTmlIcMrKOxbqjokl1Pz5mD0I9TPRkfy_Z13dvvxyflKcf3384fn1aegQBJYAO3oDXnAOQsRUq0lbzRgGo2nisghBBKiKL2LbASSvDFTRSo_VtBUtWzr7TBa02jVul_rxOOxfr3u1L3_OLXKVQ5xlLZu_kVym2_0TXQlGhASMlz9qXszYD59R6GtepHm5b3OqMfee-xZ_OAFphMRs83xuk-GOTF-fO4iaNeT9OIioppVUqUy9myqc4TYnCzQTB3Z9gXQ7W_Q02s8_-_9INeZ1kBo5m4KIfaHe3k3vz6WS2_A1rya4m</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Parrado‐Fernandez, Cristina</creator><creator>Leoni, Valerio</creator><creator>Saeed, Ahmed</creator><creator>Rodriguez‐Rodriguez, Patricia</creator><creator>Sandebring‐Matton, Anna</creator><creator>Córdoba‐Beldad, Carmen M.</creator><creator>Bueno, Paula</creator><creator>Gali, Chaitanya Chakravarthi</creator><creator>Panzenboeck, Ute</creator><creator>Cedazo‐Minguez, Angel</creator><creator>Björkhem, Ingemar</creator><general>Blackwell Publishing Ltd</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>202108</creationdate><title>Sex difference in flux of 27‐hydroxycholesterol into the brain</title><author>Parrado‐Fernandez, Cristina ; Leoni, Valerio ; Saeed, Ahmed ; Rodriguez‐Rodriguez, Patricia ; Sandebring‐Matton, Anna ; Córdoba‐Beldad, Carmen M. ; Bueno, Paula ; Gali, Chaitanya Chakravarthi ; Panzenboeck, Ute ; Cedazo‐Minguez, Angel ; Björkhem, Ingemar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5313-337fc83c70033e89456e7970b6336a8c54f11f26ee955dd30e768063b2759cd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>27‐hydroxycholesterol</topic><topic>Autopsy</topic><topic>Blood-brain barrier</topic><topic>Cerebrospinal fluid</topic><topic>CYP7B1</topic><topic>Endothelial cells</topic><topic>Gender differences</topic><topic>Gene expression</topic><topic>Medicin och hälsovetenskap</topic><topic>mRNA</topic><topic>neurodegeneration</topic><topic>Neurotoxicity</topic><topic>Oxysterols, Lifelong Health and Therapeutics–Research Papers</topic><topic>Plasma</topic><topic>Plasma levels</topic><topic>Research Paper</topic><topic>Sex</topic><topic>Sex differences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Parrado‐Fernandez, Cristina</creatorcontrib><creatorcontrib>Leoni, Valerio</creatorcontrib><creatorcontrib>Saeed, Ahmed</creatorcontrib><creatorcontrib>Rodriguez‐Rodriguez, Patricia</creatorcontrib><creatorcontrib>Sandebring‐Matton, Anna</creatorcontrib><creatorcontrib>Córdoba‐Beldad, Carmen M.</creatorcontrib><creatorcontrib>Bueno, Paula</creatorcontrib><creatorcontrib>Gali, Chaitanya Chakravarthi</creatorcontrib><creatorcontrib>Panzenboeck, Ute</creatorcontrib><creatorcontrib>Cedazo‐Minguez, Angel</creatorcontrib><creatorcontrib>Björkhem, Ingemar</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Parrado‐Fernandez, Cristina</au><au>Leoni, Valerio</au><au>Saeed, Ahmed</au><au>Rodriguez‐Rodriguez, Patricia</au><au>Sandebring‐Matton, Anna</au><au>Córdoba‐Beldad, Carmen M.</au><au>Bueno, Paula</au><au>Gali, Chaitanya Chakravarthi</au><au>Panzenboeck, Ute</au><au>Cedazo‐Minguez, Angel</au><au>Björkhem, Ingemar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sex difference in flux of 27‐hydroxycholesterol into the brain</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2021-08</date><risdate>2021</risdate><volume>178</volume><issue>16</issue><spage>3194</spage><epage>3204</epage><pages>3194-3204</pages><issn>0007-1188</issn><issn>1476-5381</issn><eissn>1476-5381</eissn><abstract>Background and Purpose
The cerebrospinal fluid (CSF)/plasma albumin ratio (QAlb) is believed to reflect the integrity of the blood–brain barrier (BBB). Recently, we reported that QAlb is lower in females. This may be important for uptake of neurotoxic 27‐hydroxycholesterol (27OH) by the brain in particular because plasma levels of 27OH are higher in males. We studied sex differences in the relation between CSF and plasma levels of 27OH and its major metabolite 7α‐hydroxy‐3‐oxo‐4‐cholestenoic acid (7HOCA) with QAlb. We tested the possibility of sex differences in the brain metabolism of 27OH and if its flux into the brain disrupted integrity of the BBB.
Experimental Approach
We have examined our earlier studies looking for sex differences in CSF levels of oxysterols and their relation to QAlb. We utilized an in vitro model for the BBB with primary cultured brain endothelial cells to test if 27OH has a disruptive effect on this barrier. We measured mRNA and protein levels of CYP7B1 in autopsy brain samples.
Key Results
The correlation between CSF levels of 27OH and QAlb was higher in males whereas, with 7HOCA, the correlation was higher in females. No significant sex difference in the expression of CYP7B1 mRNA in brain autopsy samples. A correlation was found between plasma levels of 27OH and QAlb. No support was obtained for the hypothesis that plasma levels of 27OH have a disruptive effect on the BBB.
Conclusions and Implications
The sex differences are discussed in relation to negative effects of 27OH on different brain functions.
LINKED ARTICLES
This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>33345295</pmid><doi>10.1111/bph.15353</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Wiley Free Content; Alma/SFX Local Collection |
| subjects | 27‐hydroxycholesterol Autopsy Blood-brain barrier Cerebrospinal fluid CYP7B1 Endothelial cells Gender differences Gene expression Medicin och hälsovetenskap mRNA neurodegeneration Neurotoxicity Oxysterols, Lifelong Health and Therapeutics–Research Papers Plasma Plasma levels Research Paper Sex Sex differences |
| title | Sex difference in flux of 27‐hydroxycholesterol into the brain |
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