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Detection of increased scyllo-inositol in brain with magnetic resonance spectroscopy after dietary supplementation in Alzheimer’s disease mouse models
There is evidence that inositol isomers may help protect against formation of toxic fibrils of Aβ fragments in Alzheimer's disease mouse models. Scyllo-inositol is one of the more promising inositol isomers for the potential treatment of Alzheimer’s disease (AD) and can be detected using MRS in...
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| Published in: | Neuropharmacology 2010-09, Vol.59 (4), p.353-357 |
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| creator | Choi, Ji-Kyung Carreras, Isabel Dedeoglu, Alpaslan Jenkins, Bruce G. |
| description | There is evidence that inositol isomers may help protect against formation of toxic fibrils of Aβ fragments in Alzheimer's disease mouse models. Scyllo-inositol is one of the more promising inositol isomers for the potential treatment of Alzheimer’s disease (AD) and can be detected using MRS in human subjects. In this manuscript we demonstrate using MRS, in two different mouse models of AD (APP × PS1 and APP × PS1 × tau), that we could detect increased scyllo-inositol in the hippocampus and frontal cortex in mice fed water supplemented with 16.5 mg/L of scyllo-inositol equivalent to about 3.3 mg/kg/day. We used both brain extracts using solution MRS as well as intact brain tissue using high resolution magic angle spinning (HRMAS) to ensure that any membrane-associated scyllo-inositol would be detected. By brain extracts we detected a 3.0 fold increase in scyllo-inositol in the scyllo-fed AD mice compared to normal diet (
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| doi_str_mv | 10.1016/j.neuropharm.2010.03.011 |
| format | article |
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p < 0.001). Using HRMAS we detected a 2.2–2.4-fold increase in scyllo-inositol (
p < 0.001). Scyllo-inositol treatment was associated with an increase in glutamine in hippocampus. The concentrations of scyllo-inositol were higher in the hippocampus than in the frontal cortex. Mice have a smaller concentration of scyllo-inositol than humans (ca. 100 μM vs. 500 μM in humans). Given the ease with which scyllo-inositol can be measured in human MRS data with high signal to noise ratios, these data suggest that MRS will prove useful for evaluation of inositol treatment trials in AD subjects.</description><identifier>ISSN: 0028-3908</identifier><identifier>EISSN: 1873-7064</identifier><identifier>DOI: 10.1016/j.neuropharm.2010.03.011</identifier><identifier>PMID: 20399219</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Alzheimer Disease - diet therapy ; Alzheimer Disease - metabolism ; Alzheimer’s disease ; Animals ; Brain - metabolism ; Dietary Supplements ; Disease Models, Animal ; Female ; Humans ; Inositol - administration & dosage ; Inositol - biosynthesis ; Inositol - metabolism ; Magic angle spinning ; Magnetic Resonance Spectroscopy - methods ; Mice ; Mice, Transgenic ; MRS ; Presenilin-1 - genetics ; Presenilin-1 - metabolism ; Scyllo-inositol ; Transgenic mouse</subject><ispartof>Neuropharmacology, 2010-09, Vol.59 (4), p.353-357</ispartof><rights>2010 Elsevier Ltd</rights><rights>Copyright 2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c510t-e69852c4b140d83d661a257a99a67a89e0980d32b0ee188bb94f49c00fdb612c3</citedby><cites>FETCH-LOGICAL-c510t-e69852c4b140d83d661a257a99a67a89e0980d32b0ee188bb94f49c00fdb612c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27900,27901</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20399219$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Ji-Kyung</creatorcontrib><creatorcontrib>Carreras, Isabel</creatorcontrib><creatorcontrib>Dedeoglu, Alpaslan</creatorcontrib><creatorcontrib>Jenkins, Bruce G.</creatorcontrib><title>Detection of increased scyllo-inositol in brain with magnetic resonance spectroscopy after dietary supplementation in Alzheimer’s disease mouse models</title><title>Neuropharmacology</title><addtitle>Neuropharmacology</addtitle><description>There is evidence that inositol isomers may help protect against formation of toxic fibrils of Aβ fragments in Alzheimer's disease mouse models. Scyllo-inositol is one of the more promising inositol isomers for the potential treatment of Alzheimer’s disease (AD) and can be detected using MRS in human subjects. In this manuscript we demonstrate using MRS, in two different mouse models of AD (APP × PS1 and APP × PS1 × tau), that we could detect increased scyllo-inositol in the hippocampus and frontal cortex in mice fed water supplemented with 16.5 mg/L of scyllo-inositol equivalent to about 3.3 mg/kg/day. We used both brain extracts using solution MRS as well as intact brain tissue using high resolution magic angle spinning (HRMAS) to ensure that any membrane-associated scyllo-inositol would be detected. By brain extracts we detected a 3.0 fold increase in scyllo-inositol in the scyllo-fed AD mice compared to normal diet (
p < 0.001). Using HRMAS we detected a 2.2–2.4-fold increase in scyllo-inositol (
p < 0.001). Scyllo-inositol treatment was associated with an increase in glutamine in hippocampus. The concentrations of scyllo-inositol were higher in the hippocampus than in the frontal cortex. Mice have a smaller concentration of scyllo-inositol than humans (ca. 100 μM vs. 500 μM in humans). Given the ease with which scyllo-inositol can be measured in human MRS data with high signal to noise ratios, these data suggest that MRS will prove useful for evaluation of inositol treatment trials in AD subjects.</description><subject>Alzheimer Disease - diet therapy</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer’s disease</subject><subject>Animals</subject><subject>Brain - metabolism</subject><subject>Dietary Supplements</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Humans</subject><subject>Inositol - administration & dosage</subject><subject>Inositol - biosynthesis</subject><subject>Inositol - metabolism</subject><subject>Magic angle spinning</subject><subject>Magnetic Resonance Spectroscopy - methods</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>MRS</subject><subject>Presenilin-1 - genetics</subject><subject>Presenilin-1 - metabolism</subject><subject>Scyllo-inositol</subject><subject>Transgenic mouse</subject><issn>0028-3908</issn><issn>1873-7064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqFkU1uFDEQhS0EIkPgCsg7Vj2U3T9jb5BCIIAUiQ2sLbddnfHIbTd2d9Cw4hjkepwETyYEWLGxJder98r1EUIZrBmw7uVuHXBJcdrqNK45lGeo18DYA7JiYlNXG-iah2QFwEVVSxAn5EnOOwBoBBOPyQmHWkrO5Ir8eIMzmtnFQONAXTAJdUZLs9l7HysXYnZz9KVC-6TL-dXNWzrqq4CzMzRhjkEHgzRPxSbFbOK0p3qYMVHrcNZpT_MyTR5HDLO-DSouZ_7bFt2I6ef3m1yE-ZBKx7jcnhZ9fkoeDdpnfHZ3n5LPF28_nb-vLj---3B-dlmZlsFcYSdFy03TswasqG3XMc3bjZZSdxstJIIUYGveAyITou9lMzTSAAy27xg39Sl5dfSdln5Ea8qUSXs1JTeW2VXUTv1bCW6rruK14pJ3vNsUgxd3Bil-WTDPanTZoPc6YPmPkm3TSta2UJTiqDRlTznhcJ_CQB24qp36w1UduCqoVeFaWp__PeV942-QRfD6KCirw2uHSWXjsICxLhUwykb3_5RfEaHAow</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>Choi, Ji-Kyung</creator><creator>Carreras, Isabel</creator><creator>Dedeoglu, Alpaslan</creator><creator>Jenkins, Bruce G.</creator><general>Elsevier Ltd</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>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20100901</creationdate><title>Detection of increased scyllo-inositol in brain with magnetic resonance spectroscopy after dietary supplementation in Alzheimer’s disease mouse models</title><author>Choi, Ji-Kyung ; Carreras, Isabel ; Dedeoglu, Alpaslan ; Jenkins, Bruce G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c510t-e69852c4b140d83d661a257a99a67a89e0980d32b0ee188bb94f49c00fdb612c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Alzheimer Disease - diet therapy</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer’s disease</topic><topic>Animals</topic><topic>Brain - metabolism</topic><topic>Dietary Supplements</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Humans</topic><topic>Inositol - administration & dosage</topic><topic>Inositol - biosynthesis</topic><topic>Inositol - metabolism</topic><topic>Magic angle spinning</topic><topic>Magnetic Resonance Spectroscopy - methods</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>MRS</topic><topic>Presenilin-1 - genetics</topic><topic>Presenilin-1 - metabolism</topic><topic>Scyllo-inositol</topic><topic>Transgenic mouse</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Ji-Kyung</creatorcontrib><creatorcontrib>Carreras, Isabel</creatorcontrib><creatorcontrib>Dedeoglu, Alpaslan</creatorcontrib><creatorcontrib>Jenkins, Bruce G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Ji-Kyung</au><au>Carreras, Isabel</au><au>Dedeoglu, Alpaslan</au><au>Jenkins, Bruce G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection of increased scyllo-inositol in brain with magnetic resonance spectroscopy after dietary supplementation in Alzheimer’s disease mouse models</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>59</volume><issue>4</issue><spage>353</spage><epage>357</epage><pages>353-357</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><abstract>There is evidence that inositol isomers may help protect against formation of toxic fibrils of Aβ fragments in Alzheimer's disease mouse models. Scyllo-inositol is one of the more promising inositol isomers for the potential treatment of Alzheimer’s disease (AD) and can be detected using MRS in human subjects. In this manuscript we demonstrate using MRS, in two different mouse models of AD (APP × PS1 and APP × PS1 × tau), that we could detect increased scyllo-inositol in the hippocampus and frontal cortex in mice fed water supplemented with 16.5 mg/L of scyllo-inositol equivalent to about 3.3 mg/kg/day. We used both brain extracts using solution MRS as well as intact brain tissue using high resolution magic angle spinning (HRMAS) to ensure that any membrane-associated scyllo-inositol would be detected. By brain extracts we detected a 3.0 fold increase in scyllo-inositol in the scyllo-fed AD mice compared to normal diet (
p < 0.001). Using HRMAS we detected a 2.2–2.4-fold increase in scyllo-inositol (
p < 0.001). Scyllo-inositol treatment was associated with an increase in glutamine in hippocampus. The concentrations of scyllo-inositol were higher in the hippocampus than in the frontal cortex. Mice have a smaller concentration of scyllo-inositol than humans (ca. 100 μM vs. 500 μM in humans). Given the ease with which scyllo-inositol can be measured in human MRS data with high signal to noise ratios, these data suggest that MRS will prove useful for evaluation of inositol treatment trials in AD subjects.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>20399219</pmid><doi>10.1016/j.neuropharm.2010.03.011</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | Elsevier |
| subjects | Alzheimer Disease - diet therapy Alzheimer Disease - metabolism Alzheimer’s disease Animals Brain - metabolism Dietary Supplements Disease Models, Animal Female Humans Inositol - administration & dosage Inositol - biosynthesis Inositol - metabolism Magic angle spinning Magnetic Resonance Spectroscopy - methods Mice Mice, Transgenic MRS Presenilin-1 - genetics Presenilin-1 - metabolism Scyllo-inositol Transgenic mouse |
| title | Detection of increased scyllo-inositol in brain with magnetic resonance spectroscopy after dietary supplementation in Alzheimer’s disease mouse models |
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