Role of phosphatidylinositol 3‐kinase in neuronal survival and axonal outgrowth of adult mouse dorsal root ganglia explants
- 17 October 2003
- journal article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 74 (5), 726-735
- https://doi.org/10.1002/jnr.10686
Abstract
Adult ganglionic peripheral neurons have lost dependence on target‐derived neurotrophin signaling for survival and regeneration after injury. To understand the mechanisms required to sustain such processes at maturity, we are studying neuronal survival and axonal outgrowth of adult mouse dorsal root ganglia (DRG) explants. We have here examined the role of phosphatidylinositol 3‐kinase (PI3‐K) activity. Both neuronal survival and axonal outgrowth of spontaneously growing preparations were decreased significantly by the PI3‐K inhibitor LY294002 as was the increased outgrowth caused by nerve growth factor or glial cell line‐derived factor. Inhibition of PI3‐K activity promoted neuronal cell death to the same extent in the presence as in the absence of a growth factor, whereas inhibition of mitogen‐activated protein kinase, MAPK, lacked effect. Using a compartmentalized system, it could be shown that only axonal outgrowth was decreased when the outgrowth region only was exposed to LY294002. Already‐formed growth cones showed morphological changes within 5–10 min after exposure to LY294002. Akt (PKB) is one downstream effector of PI3‐K. Immunofluorescence revealed the presence of activated Akt in DRG cell bodies and in axonal growth cones. Immunoreactivity was decreased by PI3‐K inhibition. The results suggest that Akt is constitutively active in adult DRG neurons, and that PI3‐K mediated processes are involved in neuronal survival of one or more DRG neuronal subpopulations and also in axonal elongation. The possible significance of Akt signaling for these effects is discussed.Keywords
Funding Information
- Swedish Natural Science Research Council
- Magnus Bergvalls Foundation
This publication has 55 references indexed in Scilit:
- Insulin-like growth factor I stimulates motility in human neuroblastoma cellsOncogene, 2001
- Role of PI 3-kinase, Akt and Bcl-2–related proteins in sustaining the survival of neurotrophic factor–independent adult sympathetic neuronsThe Journal of cell biology, 2001
- Growth Factor-Stimulated Phosphorylation of Akt and p70S6K Is Differentially Inhibited by LY294002 and WortmanninEndocrinology, 2001
- Spatially and Functionally Distinct Roles of the PI3-K Effector Pathway during NGF Signaling in Sympathetic NeuronsNeuron, 2000
- Regulation of Thrombin-Induced Stress Fibre Formation in Swiss 3T3 Cells by the 70-kDa S6 KinaseBiochemical and Biophysical Research Communications, 1997
- Phosphatidylinositol 3-kinase signals activate a selective subset of Rac/Rho-dependent effector pathwaysCurrent Biology, 1996
- Neurotrophins and nerve injury in the adultPhilosophical Transactions Of The Royal Society B-Biological Sciences, 1996
- Neurones and glial cells of the mouse sciatic nerve undergo apoptosis after injury in vivo and in vitroNeuroReport, 1995
- Requirement for Phosphatidylinositol-3 Kinase in the Prevention of Apoptosis by Nerve Growth FactorScience, 1995
- Nerve growth factor protects adult sensory neurons from cell death and atrophy caused by nerve injuryJournal of Neurocytology, 1987