{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T04:43:18Z","timestamp":1769834598349,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T00:00:00Z","timestamp":1489363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"University of Pennsylvania Orphan Disease Centre","award":["MPS1-13-003"],"award-info":[{"award-number":["MPS1-13-003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Gangliosides are the most complex oligosaccharide\u2010containing glycosphingolipids defined by the presence of sialic acid and although present in all tissues, predominate in the brain. Considering their importance in neural development, it is unsurprising that ganglioside metabolism is altered in neurodegenerative diseases. The severe form of mucopolysaccharidosis type I, Hurler syndrome (<jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content>), is characterised by progressive loss of neuronal function through largely undefined mechanisms. Here, we sought to interrogate brain gangliosides in a murine model of <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> and further, assessed whether dietary modulation of lipid metabolism effected correction of the metabolic abnormalities. The simple gangliosides, <jats:styled-content style=\"fixed-case\">G<jats:sub>M<\/jats:sub><\/jats:styled-content><jats:sub>2<\/jats:sub>, <jats:styled-content style=\"fixed-case\">G<jats:sub>M<\/jats:sub><\/jats:styled-content><jats:sub>3<\/jats:sub>, <jats:styled-content style=\"fixed-case\">G<jats:sub>D<\/jats:sub><\/jats:styled-content><jats:sub>2<\/jats:sub> and <jats:styled-content style=\"fixed-case\">G<jats:sub>D<\/jats:sub><\/jats:styled-content><jats:sub>3<\/jats:sub> were elevated in the five subregions examined \u2013 brain stem, cerebellum, cortex, hippocampus, subcortex \u2013 in <jats:styled-content style=\"fixed-case\">HS<\/jats:styled-content> mice as early as 2\u00a0months of age compared with their wild type counterparts. Their elevation persisted at 6\u00a0months of age, imparting protracted neurological development as these simple gangliosides have usually subsided by this stage of brain development. Their immediate synthetic precursor, lactosylceramide, was also elevated, suggesting that their increase arises at this metabolic intermediary, as dihydroceramide, ceramide and monohexosylceramide were unaffected. Dietary linoleic acid supplementation significantly reduced <jats:styled-content style=\"fixed-case\">G<jats:sub>M<\/jats:sub><\/jats:styled-content><jats:sub>2<\/jats:sub> and <jats:styled-content style=\"fixed-case\">G<jats:sub>M<\/jats:sub><\/jats:styled-content><jats:sub>3<\/jats:sub>, and furthermore, improved exploratory behaviour as assessed by the open field test, highlighting the possibility of further exploring dietary intervention as a therapeutic consideration.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13976-fig-0009-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13976","type":"journal-article","created":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T19:26:45Z","timestamp":1486495605000},"page":"287-295","source":"Crossref","is-referenced-by-count":20,"title":["Subregional brain distribution of simple and complex glycosphingolipids in the mucopolysaccharidosis type I (Hurler syndrome) mouse: impact of diet"],"prefix":"10.1111","volume":"141","author":[{"given":"Jennifer T.","family":"Saville","sequence":"first","affiliation":[{"name":"Genetics and Molecular Pathology SA Pathology at Women's and Children's Hospital North Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Ngoc","family":"Thai","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Pathology SA Pathology at Women's and Children's Hospital North Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca J.","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Pathology SA Pathology at Women's and Children's Hospital North Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ainslie L. K.","family":"Derrick\u2010Roberts","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Pathology SA Pathology at Women's and Children's Hospital North Adelaide South Australia Australia"},{"name":"School of Medicine University of Adelaide Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9092-8942","authenticated-orcid":false,"given":"Maria","family":"Fuller","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Pathology SA Pathology at Women's and Children's Hospital North Adelaide South Australia Australia"},{"name":"School of Medicine University of Adelaide Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9530-x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.4.503"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1980.tb11220.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-011-0400-y"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.06.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20355"},{"key":"e_1_2_7_9_1","first-page":"3421","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Neufeld E. 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