A role for oligodendrocyte‐derived IGF‐1 in trophic support of cortical neurons

Abstract

Neurons and glia interact in the development of mammalian central nervous systems and in the maintenance of stable myelinated axons. Recent evidence suggests a role for oligodendrocytes in providing trophic support for neurons during development and in the mature nervous system. This work prompted us to study oligodendrocyte influences on neuronal survival and death in vitro. Rat embryonic cortical neurons were co-cultured with purified oligodendrocytes at different developmental stages and separately with oligodendrocyte-conditioned medium. Neuronal survival was measured by immunocytochemistry and 3H-GABA uptake. Neurons show a marked increase in survival when co-cultured directly with oligodendrocyte precursors (OPCs) and differentiated oligodendrocytes. Neurons cultured in the presence of OPCs separated by a permeable membrane and those cultured in medium conditioned by oligodendrocytes also show a significant increase in survival. Medium conditioned by differentiated oligodendrocytes provides a greater survival effect than medium conditioned by OPCs. Neutralising antibodies to IGF-1, but not to other candidate trophic factors, block the soluble survival effect of oligodendrocytes. Cells of the oligodendrocyte lineage produce IGF-1 and recombinant IGF-1 promotes neuronal survival under identical conditions. This study provides evidence that OPCs and differentiated oligodendrocytes support neuronal survival by both contact-mediated and soluble mechanisms and that IGF-1 significantly contributes to this effect.

A Novel Role for Sema3A in Neuroprotection from Injury Mediated by Activated Microglia

“…Neuronal cell cultures were prepared from the cortices of embryonic day 16 (E16) rat embryos (Wilkins et al, 2001). After enzymatic and mechanical dissociation, cells were plated onto freshly prepared poly-L-lysine-coated 13 mm glass coverslips (1.5 ϫ 10 3 neurons per coverslip or 2.5 ϫ 10 3 neurons per coverslip) or poly-Llysine-coated plastic 6-well plates (2 million cells per well) in 2% B27-supplemented medium or insulin-free Sato-supplemented DMEM.…”

Positive feedback in the Akt/mTOR pathway and its implications for growth signal progression in skeletal muscle cells: An analytical study

“…Comparing spatial patterns of exceeded thresholds (35) to experiments that measure the result of mTOR/AKT activation (such as spatial regions of muscle growth), may therefore give insights into the quantitative kinetics (k, d 2 ) of Akt/mTOR activation and into the kinetics of Akt/mTOR inhibition by PTEN. Finally, we remark that the diffusion constant has a direct relationship to the size of the area exceeding the threshold, whereas the inhibitor tends to confine the signal to its original location.…”

“…Indeed, studies that overexpressed active AKT by genetic mutations or pharmacological activation reported an increase in muscle fibre diameter (muscular hypertrophy) while muscle fibre diameter decreased upon inhibition of Akt or mTOR (muscular atrophy) [26,3,29]. Trophic factor receptors such as IGF-1 can be randomly and anisotropically distributed along the cell surface [14,17,35] and activation of Akt by PI3K has been determined to be localised at the receptors. Therefore it remains to be understood how a signal that is associated with certain locations on the surface of a muscle cell can proceed through the entire spatial extension of this cell in a homogenous fashion.…”

Transplantation prospects for the inner retina

“…18 OPCs have also previously shown a neuroprotective capacity in vitro through neurotrophic factor secretion. 19 Thus, we were interested to know whether either of these phenomena would confer neuroprotection to RGCs upon OPC transplantation into glaucomatous eyes.…”