title: Oligodendrogenesis in iron-deficient rats: effect of apotransferrin.
abstract: In rats, iron deficiency produces an alteration in myelin formation. However, there is limited information on the effects of this condition on oligodendroglial cell (OLGc) proliferation and maturation. In the present study, we further analyzed the hypomyelination associated with iron deficiency by studying the dynamics of oligodendrogenesis. Rats were fed control (40 mg Fe/kg) or iron-deficient (4 mg Fe/kg) diets from gestation day 5 until postnatal day 3 (P3) or 11 (P11). OLGc proliferation, migration and differentiation were investigated before and after an intracranial injection of apotransferrin at 3 days of age (P3). The proliferating cell population was evaluated at P3. Iron-deficient (ID) animals showed an increase in the oligodendrocyte precursors cell (OPC) population in comparison with controls. The overall pattern of migration of cells labeled with BrdU was investigated at P11. Iron deficiency increased the amount of BrdU(+) cells in the corpus callosum (CC) and decreased OLGc maturation and myelin formation. Changes in nerve conduction were analyzed by measuring visual evoked potentials. Latency and amplitude were significantly disturbed in ID rats compared with controls. Both parameters were substantially normalized when animals were treated with a single intracranial injection of 350 ng apotransferrin (aTf). The current results give support to the idea that iron deficiency increases the number of proliferating and undifferentiated cells in the CC compared with the control. Treatment with aTf almost completely reverted the effects of iron deficiency, both changing the migration pattern and increasing the number of mature cells in the CC and myelin formation.
authors.affiliation: Instituto de Biología Celular y Neurociencias "Professor Eduardo De Robertis," Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: M V
authors.initials: MV
authors.lastname: Rosato-Siri
authors.forename: M E
authors.initials: ME
authors.lastname: Badaracco
authors.forename: E H
authors.initials: EH
authors.lastname: Ortiz
authors.forename: N
authors.initials: N
authors.lastname: Belforte
authors.forename: M Guardia
authors.initials: MG
authors.lastname: Clausi
authors.forename: E F
authors.initials: EF
authors.lastname: Soto
authors.forename: R
authors.initials: R
authors.lastname: Bernabeu
authors.forename: J M
authors.initials: JM
authors.lastname: Pasquini
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001059:Apoproteins / Q000378:metabolism / Q000627:therapeutic use*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D001921:Brain; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D003337:Corpus Callosum / Q000378:metabolism / Q000473:pathology; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D004569:Electroencephalography / Q000379:methods; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D006400:Hematocrit / Q000379:methods; D000090463:Iron Deficiencies; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D010775:Photic Stimulation / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D001059:Apoproteins; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D018809:Proliferating Cell Nuclear Antigen; D012794:Sialic Acids; D014168:Transferrin; C498633:Olig1 protein, rat; C028284:apotransferrin; C103469:polysialyl neural cell adhesion molecule