title: Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.
abstract: High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection.
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Raddatz
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Sun
authors.affiliation: Fish Disease Research Unit, University of Veterinary Medicine Hannover, Hannover, Germany.|Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Graham
authors.initials: G
authors.lastname: Brogden
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Patricia
authors.initials: P
authors.lastname: Kammeyer
authors.affiliation: Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach (Riß), Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Kalkuhl
authors.affiliation: Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach (Riß), Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Colbatzky
authors.affiliation: Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach (Riß), Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Deschl
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Naim
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Ulrich
mesh_terms: D000818:Animals; D015703:Antigens, CD; D053898:Biosynthetic Pathways / Q000235:genetics; D002490:Central Nervous System / Q000473:pathology*; D002784:Cholesterol / Q000097:blood*; D002855:Chromatography, Thin Layer; D003711:Demyelinating Diseases / Q000209:etiology*; D018752:Diet, Fat-Restricted; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000150:complications / Q000378:metabolism / Q000821:virology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D008099:Liver / Q000378:metabolism; D051379:Mice; D046228:Microarray Analysis; D020127:Recovery of Function / Q000502:physiology*; D017945:Theilovirus / Q000502:physiology; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D002784:Cholesterol
keywords: Paigen diet; Theiler's murine encephalomyelitis; cholesterol biosynthesis; high-performance thin layer chromatography; hypercholesterolemia; microarray; multiple sclerosis