Differential effects of apotransferrin on two populations of oligodendroglial cells

Abstract

In the central nervous system (CNS), apotransferrin (aTf) is produced by oligodendroglial cells (OLGcs), and aTf is essential for cell survival. We previously demonstrated that a single intracranial injection of aTf in 3-day-old rats accelerates differentiation of OLGc and that aTf acts at early stages of development on certain populations of OLGcs, promoting accelerated maturation, with no effect on late markers of cell differentiation. The objective of the present study was to analyze OLGc maturation at two different stages of rat development, 4 and 10 days of age, in OLGcs isolated from the brain after intracranial injection of aTf at 3 days of age, and to explore the in vitro effect of aTf added to cultures of OLGc isolated from aTf-injected and control brains. The maturational cell stages were identified by immunocytochemistry with different OLGc markers and by analysis of their morphological complexity. The OLGcs isolated from 4- and 10-day-old animals intracranially injected with aTf were more differentiated than control cells. Treatment with aTf of the cultures of OLGcs that were isolated from 4-day-old saline-injected control animals induced their differentiation, while a similar treatment of the cultures of OLGcs that were isolated from 10-day-old animals did not induce further maturation of the cells. The results presented in the present report demonstrate that the in vivo effects of aTf on OLGc maturation can be reproduced in cultures and that the effects of aTf occur early in development during a narrow, transient "temporal window" within which OLGcs are sensitive to its action.

Deficit of pericapillary oligodendrocytes in the prefrontal cortex in schizophrenia

“…Pericapillary oligodendrocytes associated with BBB provide an effective regulatory point for iron movement from the plasma pool to the brain parenchyma. They contain iron and the proteins involved in iron uptake (transferrin and transferrin receptor) and intracellular storage (ferritin) (Burdo et al1999;Moos et al 2001;Garcia et al 2003). Decreased brain iron levels have been related to impaired dopaminergic function and have been reported in restless legs syndrome, clinically overlapping with schizophrenia (Barriere et al 2005;Hogl and Poewe 2005).…”

Transferrin and thyroid hormone converge in the control of myelinogenesis

“…This fact has been strengthened by studies of our group related to the action of a single intracerebral injection of this glycoprotein in young rats (Escobar Cabrera et al, 1994. The in vivo effects of aTf have also been reproduced in OLG primary cultures (García et al, 2003(García et al, , 2004(García et al, , 2007Perez et al, 2009Perez et al, , 2013 and in the N19 and N20.1 oligodendroglial cell lines (Paez et al, , 2005(Paez et al, , 2006. More recent results suggest that aTf participates in the control of OLG differentiation by two converging regulatory mechanisms: in the presence of mitogens, aTf promotes the commitment of undifferentiated NPCs to OLG lineage and, after mitogen withdrawal, aTf seems to promote OLG terminal maturation (Silvestroff et al, 2012).…”

Oligodendrocytes and myelination: The role of iron

“…The differentiation process is mediated by the transferrin receptor and by different signal transduction molecules, with the participation of the cytoskeleton. Increase in cAMP and CREB phosphorylation occurs when Tf is added to OLGcs in culture and/or when transferrin is intracranially injected in newborn rats Garcia et al, 2003).…”