Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin.
Twenty-one-day-old Wistar rats were fed a diet containing 0.6% cuprizone for 2 weeks. Studies carried out after withdrawal of cuprizone showed histological evidences of marked demyelination in the corpus callosum. Biochemical studies of isolated myelin showed a marked decrease in myelin proteins, phospholipids, and galactocerebrosides as well as a marked decrease in myelin yield. Treatment of these animals with a single intracranial injection of 350 ng of apotransferrin at the time of withdrawal of cuprizone induced a marked increase in myelin deposition resulting in a significantly improved remyelination, evaluated by histological, immunocytochemical, and biochemical parameters, in comparison to what was observed in spontaneous recovery. Immunocytochemical studies of cryotome sections to analyze developmental parameters of the oligodendroglial cell population at the time of termination of cuprizone and at different times thereafter showed that in the untreated animals, there was a marked increase in the number of NG2-BrdU-positive precursor cells together with a marked decrease in MBP expression at the peak of cuprizone-induced demyelination. As expected, the amount of precursor cells decreased markedly during spontaneous remyelination and was accompanied by an increase in MBP reactivity. In the apotransferrin-treated animals, these phenomena occurred much faster, and remyelination was much more efficient than in the untreated controls. The results of this study suggest that apotransferrin is a very active promyelinating agent which could be important for the treatment of certain demyelinating conditions.
Adamo
A M
AM
Instituto de Química y Físicoquímica Biológica (IQUIFIB), UBA-CONICET and Departamento de Química Biológica, Facultad de Farmacia y Bioquímica. Junín 956, Buenos Aires C1113AAD, Argentina.
Paez
P M
PM
Escobar Cabrera
O E
OE
Wolfson
M
M
Franco
P G
PG
Pasquini
J M
JM
Soto
E F
EF
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001059:Apoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D003471:Cuprizone; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004347:Drug Interactions; D038983:Galactolipids / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014168:Transferrin / Q000494:pharmacology / Q000627:therapeutic use*; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D001059:Apoproteins; D001973:Bromodeoxyuridine; D039481:CD11b Antigen; D003471:Cuprizone; D003598:Cytoskeletal Proteins; D038983:Galactolipids; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D004676:Myelin Basic Protein; D011509:Proteoglycans; D014168:Transferrin; D000099216:Chondroitin Sulfate Proteoglycan 4; C028284:apotransferrin; C007293:DAPI