title: Selective normalisation of regional brain bis(monoacylglycero)phosphate in the mucopolysaccharidosis 1 (Hurler) mouse.
abstract: Bis(monoacylglycero)phosphate (BMP) is a glycerophospholipid highly enriched in the lysosomal network and elevated in lysosomal diseases. To correct this elevation, BMP synthesis was manipulated by dietary fatty acid supplementation and the impact on subregional brain BMP and pathology assessed in the mouse model of mucopolysaccharidosis 1 (Hurler syndrome (HS)). There was widespread elevation of BMP in HS mice across all six sub-regions - brain stem, cortex, cerebellum, hippocampus, olfactory bulb and the sub-cortex - with 22:6/22:6 the most abundant species. Linoleic acid normalised total BMP in all regions except the cortex and cerebellum, although there were differences in fatty acid species; the major finding a decrease in 22:6- and a concomitant increase in 22:5-containing species. A battery of behaviour assessments showed that in the water cross maze both HS and wild type mice performed less well on the linoleic acid diet, and that both HS and wild type mice on the linoleic acid diet performed similarly and better in the exploratory open field test. This may be a consequence of differential subregional BMP composition in the brain. The effects of high fat and docosahexaenoic/eicosapentaenoic acid enriched diets were generally unremarkable. Although major pathologies were not completely abrogated, much of the neurobehavioural testing was confounded by skeletal pathology that did not resolve. This is the first detailed characterisation of subregional brain BMP species informing on the ability to manipulate this phospholipid in the brain, and as such, may hold promise as an adjunct therapy not only for HS but also for other lysosomal diseases.
authors.affiliation: Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia 5006, Australia.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Saville
authors.affiliation: Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia 5006, Australia.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Lehmann
authors.affiliation: Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia 5006, Australia,; Department of Paediatrics, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Ainslie L K
authors.initials: ALK
authors.lastname: Derrick-Roberts
authors.affiliation: Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia 5006, Australia,; Department of Paediatrics, University of Adelaide, Adelaide, South Australia 5005, Australia. Electronic address: maria.fuller@adelaide.edu.au.
authors.forename: Maria
authors.initials: M
authors.lastname: Fuller
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000473:pathology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006025:Glycosaminoglycans / Q000652:urine; D007068:Iduronidase / Q000172:deficiency / Q000235:genetics*; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050178:Monoglycerides / Q000378:metabolism*; D009043:Motor Activity / Q000235:genetics; D008059:Mucopolysaccharidosis I / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D012737:Sex Factors
chemical_list: D006025:Glycosaminoglycans; D008246:Lysophospholipids; D050178:Monoglycerides; C012786:bis(monoacylglyceryl)phosphate; D007068:Iduronidase
keywords: Diet; Fatty acid; Hurler syndrome; Linoleic acid; Lysosomal disease; Mouse model; Mucopolysaccharidosis 1; Neurobehaviour; Phospholipid; Therapy