Retrograde Support of Neuronal Survival without Retrograde Transport of Nerve Growth Factor

• Published in: Science (American Association for the Advancement of Science) Vol. 295; no. 5559; pp. 1536 - 1539
• Main Authors: MacInnis, Bronwyn L., Campenot, Robert B.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 22.02.2002; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Akt protein; Animals; Antibodies; Axons; Axons - metabolism; Biological and medical sciences; Biology; Brain research; Cell physiology; Cell Survival - drug effects; Cells, Cultured; Chromones - pharmacology; Cross-Linking Reagents; Cultural groups; Cultured cells; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Ganglia; Genetic aspects; Growth; Growth factor receptors; Inhibition; Iodine Radioisotopes; Memory interference; Microspheres; Mitogen-Activated Protein Kinases - metabolism; Molecular and cellular biology; Morpholines - pharmacology; Nerve Growth Factor - metabolism; Nerve Growth Factor - pharmacology; Nerves; Neurons; Neurons - metabolism; Neurons - physiology; Neuroscience; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein Transport; Protein-Serine-Threonine Kinases; Proteins; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Receptor, trkA - metabolism; Responses to growth factors, tumor promotors, other factors; Signal Transduction; Superior Cervical Ganglion; Canada; Nerve growth factor; Neuron; Sympathetic nervous system; Autonomic nervous system; In vitro; Survival
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1064913

Application of nerve growth factor (NGF) covalently cross-linked to beads increased the phosphorylation of TrkA and Akt, but not of mitogen-activated protein kinase, in cultured rat sympathetic neurons. NGF beads or iodine-125-labeled NGF beads supplied to distal axons resulted in the survival of over 80% of the neurons for 30 hours, with little or no retrograde transport of iodine-125-labeled NGF; whereas application of free iodine-125-labeled NGF (0.5 nanograms per milliliter) produced 20-fold more retrograde transport, but only 29% of the neurons survived. Thus, in contrast to widely accepted theory, a neuronal survival signal can reach the cell bodies unaccompanied by the NGF that initiated it.