How do the satellite glia cells of the dorsal root ganglia respond to stressed neurons?--nitric oxide saga from embryonic development to axonal injury in adulthood

Abstract

Dorsal root ganglia (DRG) respond to peripheral nerve injury by up-regulating nitric oxide (NO) production by neurons and glia in addition to local fibroblasts, endothelium and macrophages. We hypothesise that NO produced from these cells has specific roles. We have shown that when neuronal NO synthase (nNOS) is blocked in axotomised DRG, neurons undergo degenerative changes (Thippeswamy et al., 2001, 2007a). Further, we demonstrated that increased neuronal NO production, in response to axotomy/growth factor-deprivation in vitro, signals glial cells to produce trophic factors to support neuronal survival (Thippeswamy et al., 2005a). Recently, we found that treating satellite glia-neuron co-cultures with nNOS inhibitor, 7-nitroindazole (7NI), decreases the number of nestin+ cells that show neuron-like morphology. Cultured/axotomised DRG also upregulate inducible NOS (iNOS) in non-neuronal cells. Therefore, it is plausible that degenerative changes following nNOS inhibition are also due to iNOS-mediated excessive NO production by non-neuronal cells, which indeed is cytotoxic. NG-nitro-l-arginine methylester (L-NAME), the pan NOS inhibitor did not significantly change nNOS+ neuron number in axotomised DRG compared to 7NI suggesting that iNOS-mediated NO contributes to the degenerative process. In this paper, these findings from our and others' past work on NO-mediated neuron-glia signalling in axotomised DRG are discussed.