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Glial‐mediated neuroprotection: Evidence for the protective role of the NO‐cGMP pathway via neuron–glial communication in the peripheral nervous system
Author(s) -
Thippeswamy Thimmasettappa,
Mckay Jennifer S.,
Morris Richard,
Quinn John,
Wong LiangFong,
Murphy David
Publication year - 2004
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20105
Subject(s) - biology , axotomy , neuroprotection , schwann cell , neuroscience , neuroglia , neurotrophin , dorsal root ganglion , microbiology and biotechnology , nerve growth factor , peripheral nervous system , neurotrophin 3 , neurotrophic factors , central nervous system , receptor , brain derived neurotrophic factor , biochemistry , spinal cord
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. © 2004 Wiley‐Liss, Inc.