Intracellular events mediating insulin‐like growth factor I‐induced oligodendrocyte development: modulation by cyclic AMP

Abstract

Insulin-like growth factor I (IGF-I) is a potent inducer of oligodendrocyte development and myelination. Although IGF-I intracellular signaling has been well described in several cell types, intracellular mechanisms for IGF-I-induced oligodendrocyte development have not been defined. By using specific inhibitors of intracellular signaling pathways, we report here that the MAPK and phosphatidylinositol 3-kinase signaling pathways are required for the full effect of IGF-I on oligodendrocyte development in primary mixed rat cerebrocortical cell cultures. The MAPK activation, but not the phosphatidylinositol 3-kinase activation, leads to phosphorylation of the cAMP response element-binding protein, which is necessary for IGF-I to induce oligodendrocyte development. cAMP, although it does not show any effect on oligodendrocyte development, has an inhibitory effect on IGF-I-induced oligodendrocyte development that is mediated by the cAMPdependent protein kinase. Furthermore, cAMP also has an inhibitory effect on IGF-I-dependent MAPK activation. This is a cAMP-dependent protein kinase-independent effect and probably contributes to the cAMP action on IGF-I-induced oligodendrocyte development.

Elevated Phosphatidylinositol 3,4,5-Trisphosphate in Glia Triggers Cell-Autonomous Membrane Wrapping and Myelination

“…In the CNS, enhanced myelin sheath thickness has been seen in transgenic mice overexpressing IGF-1 (Carson et al, 1993). Given that IGF-1 receptors are expressed by oligodendrocytes and signal via PI3K and MAPK (mitogen-activated protein kinase) pathways at least in vitro (Palacios et al, 2005;Bibollet-Bahena and Almazan, 2009), IGF-1 would be a candidate to stimulate myelin formation via PI3K downstream signaling. However, we note that oligodendrocytes also respond with hypermyelination to elevated NRG1 expression, although NRG1 is dispensable for normal CNS myelin formation (Brinkmann et al, 2008).…”

Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes

“…In the present study ERK1/2, but not PI-3K, pathway was required for QUE-induced differentiation of NPCs into Oligs (Figure 3 and Supplementary Figure 2), whereas both signaling pathways were required for the full effect of IGF-I on Olig development in primary mixed rat cerebrocortical cell cultures. 37 Oligs produce myelin membranes that wrap around axons and are interspersed by unmyelinated nodes that permit salutatory conduction of nerve impulses. These cells progress through several stages starting from the expression of particular Olig-associated genes such as CNP.…”

Hyperforin promotes mitochondrial function and development of oligodendrocytes

“…By increasing the monoaminergic neurotransmission, chronic antidepressant treatment increases cAMP and upregulates the function and expression of the transcription factor CREB, which can increase the expressions of neurotrophic factors (Duman, 2002). Expression of IGF-I could also be increased by modulating cAMP levels (Palacios et al, 2005). A recent study has shown that chronic treatment of fluoxetine increases the levels of both IGF-1 mRNA and IGF-I receptors in the frontal cortex but not the hippocampus in rat brains (Grunbaum-Novak et al, 2008).…”