Cell death in the oligodendrocyte lineage

Abstract

We have recently found that about 50% of newly formed oligodendrocytes normally die in the developing rat optic nerve. When purified oligodendrocytes or their precursors are cultured in the absence of serum or added signalling molecules, they die rapidly with the characteristics of programmed cell death. This death is prevented either by the addition of medium conditioned by cultures of their normal neighboring cells in the developing optic nerve, or by the addition of platelet-derived growth factor (PDGF) or insulin-like growth factors (IGFs). Increasing PDGF in the developing optic nerve decreases normal oligodendrocyte death by up to 90% and doubles the number of oligodendrocytes, suggesting that this normally occurring glial cell death might result from a competition for limiting amounts of survival signals. These results suggest that competition for limiting amounts of survival factors is not confined to developing neurons, and raise the possibility that a similar mechanism may be responsible for some naturally occurring cell deaths in nonneural tissues.

A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells

“…More generally, these observations indicate that the microenvironment of OPCs plays a critical role in the development of these cells. This notion is consistent with findings that ECM components can regulate the proliferative response of OPCs after treatment with PDGF-AA (23), the main growth factor responsible for OPC proliferation (24,25).…”

Recombinant EPF/chaperonin 10 promotes the survival of O4-positive pro-oligodendrocytes prepared from neonatal rat brain

“…Cell viability at the beginning of the single cell culturing period was 75.0%±4.1. As previously observed (Barres et al 1992a;Barres et al 1992b), oligodendrocyte viability declined rapidly in the absence of growth factors, so that after 20 hours of culture the cell viability was 23.6±3.0%. IGF-1 (Fig.…”

“…For definitive assays of oligodendrocyte survival, singlecell experiments are preferred (Barres et al 1992b). O4 + oligodendrocytic cells were used in survival assays since cells of this stage of the oligodendrocyte lineage have the ability to divide and may be involved in the remyelination of axons in the CNS following brain injury (Gard and Pfeiffer 1993;Amat et al 1998;Keirstead and Blakemore 1999).…”

“…Control cultures received defined medium (5 μl of 2×) alone. Cell survival was assessed at the commencement of culture and after 20 and 44 hours of culture using MTT reagent as described above (Barres et al 1992b).…”

Continued Administration of Ciliary Neurotrophic Factor Protects Mice from Inflammatory Pathology in Experimental Autoimmune Encephalomyelitis

“…In vitro CNTF promotes the survival of neurons 20,58 and reduces tumor necrosis factor-␣ and serum deprivationinduced cell death of oligodendrocytes. 19,59,60 In vivo, it prevents the degeneration of axotomized neurons. 23 In CNTF-deficient mice induction of EAE with MOG peptide results in more severe axonal damage, increased number of apoptotic oligodendrocytes, and a reduction in proliferating oligodendrocyte progenitor cells compared to WT mice.…”