Factors contributing to neurotrophin-independent survival of adult sensory neurons.
Dorsal root ganglion (DRG) sensory neurons become less dependent upon neurotrophins for their survival as they mature. DRG neurons from young adult rats were dissociated and cultured in vitro in serum-free defined medium. We show that adult DRG sensory neurons are able to survive for at least 2 weeks in culture in the absence of nerve growth factor (NGF). We then investigated potential mechanisms contributing to this apparent neurotrophin-independent survival in these neurons through the use of inhibitors of cellular signaling pathways. The phosphoinositide kinase-3 (PI 3-K) inhibitor LY294002, and a protein kinase C (PKC) inhibitor, chelerythrine resulted in significant decreases in neuronal survival. Neither the mitogen activated protein kinase kinase (MEK) inhibitor U0126 nor two other PKC inhibitors (bisindolylmaleimide and rottlerin) had any significant effect on survival. Our results point to the importance of PI 3-K and PKC signaling in the neurotrophin-independent survival of adult DRG neurons.
Dodge
M Elaine
ME
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, NF A1B 3V6 Canada.
Rahimtula
Masuma
M
Mearow
Karen M
KM
D000367:Age Factors; D000470:Alkaloids; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053119:Benzophenanthridines; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000166:cytology* / Q000502:physiology*; D010617:Phenanthridines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D000470:Alkaloids; D053119:Benzophenanthridines; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D010617:Phenanthridines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D020932:Nerve Growth Factor; C016299:chelerythrine; D011493:Protein Kinase C