Abstract
The NO-cGMP pathway has emerged as a neuroprotective signaling system involved in communication between neurons and glia. We have previously shown that axotomy or nerve growth factor (NGF)-deprivation of dorsal root ganglion (DRG) neurons leads to increased production of NO and at the same time an increase in cGMP production in their satellite glia cells. Blockade of NO or its receptor, the cGMP synthesizing enzyme soluble guanylate cyclase (sGC), results in apoptosis of neurons and glia. We now show that co-culture of neonatal DRG neurons with either Schwann cells pre-treated with an NO donor or a membrane-permeant cGMP analogue; or neurons maintained in the medium from Schwann cell cultures treated in the same way, prevents neuronal apoptosis. Both NO donor and cGMP treatment of Schwann cells results in synthesis of NGF and NT3. Furthermore, if the Schwann cells are previously infected with adenoviral vectors expressing a dominant negative sGC mutant transgene, treatment of these Schwann cells with an NO donor now fails to prevent neuronal apoptosis. Schwann cells treated in this way also fail to express neither cGMP nor neurotrophins. These findings suggest NO-sGC-cGMP-mediated NGF and NT3 synthesis by Schwann cells protect neurons.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Apoptosis / drug effects
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Apoptosis / physiology
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Cell Communication / physiology
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Cells, Cultured
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Coculture Techniques
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Culture Media, Conditioned / pharmacology
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Cyclic GMP / analogs & derivatives
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Cyclic GMP / metabolism*
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Cyclic GMP / pharmacology
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Cytoprotection
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Ganglia, Spinal / drug effects
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Ganglia, Spinal / metabolism
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Guanylate Cyclase
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Nerve Degeneration / metabolism
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Nerve Degeneration / prevention & control
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Neuroglia / metabolism*
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Neurons / metabolism*
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Neurons, Afferent / drug effects
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Neurons, Afferent / metabolism
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Neuroprotective Agents / metabolism*
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Nitric Oxide / metabolism*
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Nitric Oxide Donors / pharmacology
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Peripheral Nervous System / cytology
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Peripheral Nervous System / metabolism*
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Rats
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Rats, Wistar
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Receptor, Nerve Growth Factor / drug effects
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Receptor, Nerve Growth Factor / metabolism
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Receptor, trkC / drug effects
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Receptor, trkC / metabolism
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Receptors, Cytoplasmic and Nuclear / genetics
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Schwann Cells / drug effects
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Schwann Cells / metabolism
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Signal Transduction / genetics
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Signal Transduction / physiology
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Soluble Guanylyl Cyclase
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Transfection
Substances
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Culture Media, Conditioned
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Neuroprotective Agents
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Nitric Oxide Donors
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Receptor, Nerve Growth Factor
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Receptors, Cytoplasmic and Nuclear
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Nitric Oxide
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Receptor, trkC
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Guanylate Cyclase
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Soluble Guanylyl Cyclase
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Cyclic GMP