title: Vitamin B₁₂ dependent changes in mouse spinal cord expression of vitamin B₁₂ related proteins and the epidermal growth factor system.
abstract: Chronic vitamin B12 (cobalamin) deficiency in the mammalian central nervous system causes degenerative damage, especially in the spinal cord. Previous studies have shown that cobalamin status alters spinal cord expression of epidermal growth factor (EGF) and its receptor in rats. Employing a mouse model of cobalamin-depletion and loading, we have explored the influence of Cbl status on spinal cord expression of cobalamin related proteins, as well as all four known EGF receptors and their activating ligands. Following four weeks of osmotic minipump infusion (n=7 in each group) with cobinamide (4.25nmol/h), saline or cobalamin (1.75nmol/h) the spinal cords were analyzed for cobalamin and for the mRNA levels of cobalamin related proteins and members of the EGF system using quantitative reverse transcription PCR. The median spinal cord cobalamin content was 17, 32, and 52pmol/gr of tissues in cobinamide, saline, and cobalamin treated animals, respectively. Both cobinamide and cobalamin induced a significant decrease in the expression of the lysosomal membrane cobalamin transporter. All four EGF receptors and their activating ligands, except for EGF, were expressed in the spinal cord. Notably, the expression of one of the EGF receptors, HER3, and the ligands heparin-binding EGF-like growth factor, transforming growth factor-α, and neuregulins 1α was increased in cobalamin treated mice. Our studies show that four weeks treatment of mice with cobinamide induces spinal cord cobalamin depletion and that cobalamin loading induces an altered expression pattern of the EGF system thus confirming a spinal cord cross talk between Cbl and the EGF system.
authors: Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus, Denmark. elena.mutti@libero.it
authors: Elena
authors: E
authors: Mutti
authors: Dorte L
authors: DL
authors: Lildballe
authors: Lise
authors: L
authors: Kristensen
authors: Henrik
authors: H
authors: Birn
authors: Ebba
authors: E
authors: Nexo
mesh_terms: D000818:Animals; D003038:Cobamides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D020880:Neuregulins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects*; D014805:Vitamin B 12 / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D003038:Cobamides; D020880:Neuregulins; D012333:RNA, Messenger; D014803:Vitamin B Complex; C017142:cobinamide; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D014805:Vitamin B 12