Abstract
Neurite outgrowth is important in neuronal circuit formation and functions, and for regeneration of neuronal networks following trauma and disease in the brain. Thus, identification and characterization of the molecules that regulate neurite outgrowth are essential for understanding how brain circuits form and function and for the development of treatment of neurological disorders. In this study, we found that structurally different lysophosphatidylethanolamine (LPE) species, palmitoyl-LPE (16:0 LPE) and stearoyl-LPE (18:0 LPE), stimulate neurite growth in cultured cortical neurons. Interestingly, YM-254890, an inhibitor of Gq/11 protein, inhibited 16:0 LPE-stimulated neurite outgrowth but not 18:0 LPE-stimulated neurite outgrowth. In contrast, pertussis toxin, an inhibitor of Gi/Go proteins, inhibited 18:0 LPE-stimulated neurite outgrowth but not 16:0 LPE-stimulated neurite outgrowth. The effects of protein kinase C inhibitors on neurite outgrowth were also different. In addition, both 16:0 LPE and 18:0 LPE activate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2, but the effect of the MAPK inhibitor differed between the 16:0 LPE- and 18:0 LPE-treated cultures. Collectively, the results suggest that the structurally different LPE species, 16:0 LPE and 18:0 LPE stimulate neurite outgrowth through distinct signaling cascades in cultured cortical neurons and that distinct G protein-coupled receptors are involved in these processes.
Highlights
Neurite outgrowth is important in neuronal wiring during development and synaptic plasticity under physiological conditions, and in the regeneration of neuronal wiring following trauma and disease in the brain [1, 2]
When the cultured cortical neurons were incubated with 1 μM egg yolk LPE for 11days, the tau and microtubule-associated protein 2 (MAP2) signals area were significantly increased compared to those in the control cultures (Fig. 1A-C)
These results suggest that egg yolk LPE strongly stimulates both axonal and dendritic outgrowth in cultured cortical neurons
Summary
Neurite outgrowth is important in neuronal wiring during development and synaptic plasticity under physiological conditions, and in the regeneration of neuronal wiring following trauma and disease in the brain [1, 2]. Several extracellular ligands that regulate the neurite outgrowth of central nervous system (CNS) neurons have been identified. These ligands are varied and include neurotrophins, Wnt proteins, neurotransmitters, neuropeptides [1,2,3]. Phospholipids are amphiphilic molecules with a hydrophilic head esterified by a hydrophobic fatty acid chain. They play crucial roles in various biological processes, ranging from structural integrity of cellular and organelle membranes, to intracellular signal transduction [4]. A few studies suggest the cell-type specific roles of LPE in cultures [9–
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