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The role of glial cells in influencing neurite extension by dorsal root ganglion cells

  • Kai-Yu Ng (a1), Yung H. Wong (a2) and Helen Wise (a1)

When pretreated with pertussis toxin (PTX), the neurites of adult rat dorsal root ganglion (DRG) cells in mixed cell cultures retract over a period of 2 h following the initial stimulus of removal from the cell culture incubator for brief periods of observation. The purpose of this investigation was to determine whether this PTX-dependent response was specific to any one of the three subpopulations of DRG neurons. However, no neurite retraction response was observed in neuron-enriched populations of cells, or in cultures enriched in isolectin B4 (IB4)-positive neurons or in IB4-negative neurons. But, the addition of non-neuronal cells, and/or medium conditioned by non-neuronal cells, was sufficient to restore the PTX-dependent neurite retraction response, but only in large diameter IB4-negative neurons. In conclusion, we have identified a regulatory response, mediated by Gi/o-proteins, which prevents retraction of neurites in large diameter IB4-negative cells of adult rat DRG. The non-neuronal cells of adult rat DRG constitutively release factor/s that can stimulate neurite retraction of a subset of isolated DRG neurons, but this property of non-neuronal cells is only observed when the Gi/o-proteins of large diameter IB4-negative cells are inhibited.

Corresponding author
Correspondence should be addressed to: Helen Wise, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China phone: +852 2603 6849 fax: +852 2603 5139 email:
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Bennett, D.L., Michael, G.J., Ramachandran, N., Munson, J.B., Averill, S., Yan, Q. et al. (1998) A distinct subgroup of small DRG cells express GDNF receptor components and GDNF is protective for these neurons after nerve injury. Journal of Neuroscience 18, 30593072.
Campana, W.M. (2007) Schwann cells: activated peripheral glia and their role in neuropathic pain. Brain Behavior and Immunity 21, 522527.
Clarke, G.A. and Moss, D.J. (1997) GP55 inhibits both cell adhesion and growth of neurons, but not non-neuronal cells, via a G-protein-coupled receptor. European Journal of Neuroscience 9, 334341.
Dublin, P. and Hanani, M. (2007) Satellite glial cells in sensory ganglia: their possible contribution to inflammatory pain. Brain Behavior and Immunity 21, 592598.
Fang, X., Djouhri, L., McMullan, S., Berry, C., Waxman, S.G., Okuse, K. et al. (2006) Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9 expression. Journal of Neuroscience 26, 72817292.
Fields, R.D. and Stevens-Graham, B. (2002) New insights into neuron–glia communication. Science 298, 556562.
Filippo, M.D., Sarchielli, P., Picconi, B. and Calabresi, P. (2008) Neuroinflammation and synaptic plasticity: theorectical basis for a novel, immune-centred, therapeutic approach to neurological disorders. Trends in Pharmacological Sciences 29, 402412.
Franklin, S.L., Davies, A.M. and Wyatt, S. (2009) Macrophage stimulating protein is a neurotrophic factor for a sub-population of nociceptive sensory neurons. Molecular and Cellular Neuroscience 41, 175185
Gavazzi, I., Kumar, R.D.C., McMahon, S.B. and Cohen, J. (1999) Growth responses of different subpopulations of adult sensory neurons to neurotrophic factors in vitro. European Journal of Neuroscience 11, 34053414.
Guseva, D. and Chelyshev, Y. (2006) The platicity of the DRG neurons belonging to different subpopulations after dorsal rhizotomy. Cellular and Molecular Neurobiology 26, 12251234.
Hanani, M. (2005) Satellite glial cells in sensory ganglia: from form to function. Brain Research Reviews 48, 457476.
He, J.C.J., Gomes, I., Nguyen, T., Jayaram, G., Ram, P.T., Devi, L.A. et al. (2005) The Gαo/i-coupled cannabinoid receptor-mediated neurite outgrowth involves rap regulation of Src and Stat3. Journal of Biological Chemistry 280, 3342633434.
He, J.C.J., Neves, S.R., Jordan, J.D. and Iyengar, R. (2006) Role of the Go/i signaling network in the regulation of neurite outgrowth. Canadian Journal of Physiology and Pharmacology 84, 687694.
Heblich, F., England, S. and Docherty, R.J. (2001) Indirect actions of bradykinin on neonatal rat dorsal root ganglion neurones: a role for non-neuronal cells as nociceptors. Journal of Physiology 536, 111121.
Igarashi, M., Strittmatter, S.M., Vartanian, T. and Fishman, M.C. (1993) Mediation by G proteins of signals that cause collapse of growth cones. Science 259, 7779.
Julius, D. and Basbaum, A.I. (2001) Molecular mechanisms of nociception. Nature 413, 203210.
Kimpinski, K. and Mearow, K. (2001) Neurite growth promotion by nerve growth factor and insulin-like growth factor-1 in cultured adult sensory neurons: role of phosphoinositide 3-kinase and mitogen activated protein kinase. Journal of Neuroscience 63, 486499.
Kindt, R.M. and Lander, A.D. (1995) Pertussis toxin specifically inhibits growth cone guidance by a mechanism independent of direct G protein inactivation. Neuron 15, 7988.
Leclere, P.G., Norman, E., Groutsi, F., Coffin, R., Mayer, U., Pizzey, J. et al. (2007) Impaired axonal regeneration by isolectin B4-binding dorsal root ganglion neurons in vitro. Journal of Neuroscience 27, 11901199.
Lindsay, R.M. (1988) Nerve growth factors (NGF, BDNF) enhance axonal regeneration but are not required for survival of adult sensory neurons. Journal of Neuroscience 8, 23942405.
Lotto, B., Upton, L., Price, D.J. and Gaspar, P. (1999) Serotonin receptor activation enhances neurite outgrowth of thalamic neurones in rodents. Neuroscience Letters 269, 8790.
Lu, X. and Richardson, P.M. (1991) Inflammation near the nerve cell body enhances axonal regeneration. Journal of Neuroscience 11, 972978.
Molliver, D.C., Wright, D.E., Leitner, M.L., Parsadanian, A.S., Doster, K., Wen, D. et al. (1997) IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life. Neuron 19, 849861.
Nascimento, R.S., Santiago, M.F., Marques, S.A., Allodi, S. and Martinez, A.M.B. (2008) Diversity among satellite glial cells in dorsal root ganglia of the rat. Brazilian Journal of Medical Biology Research 41, 10111017.
Nave, K.A. and Trapp, B.D. (2008) Axon–glial signaling and the glial support of axon function. Annual Review of Neuroscience 31, 535561.
Priestley, J.V., Michael, G.J., Averill, S., Liu, M. and Willmott, N. (2002) Regulation of nociceptive neurons by nerve growth factor and glial cell line derived neurotrophic factor. Canadian Journal of Physiology and Pharmacology 80, 495505.
Raye, W.S., Tochon-Danguy, N., Pouton, C.W. and Haynes, J.M. (2007) Heterogeneous population of dopaminergic neurons derived from mouse embryonic stem cells: preliminary phenotyping based on receptor expression and function. European Journal of Neuroscience 25, 19611970.
Rowlands, D.K., Kao, C.L. and Wise, H. (2001) Regulation of prostacyclin and prostaglandin E2 receptor mediated responses in adult rat dorsal root ganglion cells, in vitro. British Journal of Pharmacology 133, 1322.
Snider, W.D. and McMahon, S.B. (1998) Tackling pain at the source: new ideas about nociceptors. Neuron 20, 629632.
Strittmatter, S.M., Fishman, M.C. and Zhu, X.-P. (1994) Activated mutants of the α subunit of Go promote an increased number of neurites per cell. Journal of Neuroscience 14, 23272338.
Stucky, C.L. and Lewin, G.R. (1999) Isolectin B4-positive and -negative nociceptors are functionally distinct. Journal of Neuroscience 19, 64976505.
Swarzenski, B.C., O'Malley, K.L. and Todd, R.D. (1996) PTX-sensitive regulation of neurite outgrowth by the dopamine D3 receptor. NeuroReport 7, 573576.
Tamura, M., Nogimori, K., Murai, S., Yajima, M., Ito, K., Katada, T. et al. (1982) Subunit structure of islet-activating protein, pertussis toxin, in comformity with the A-B model. Biochemistry 21, 55165522.
Tang, H.B., Li, Y.S. and Nakata, Y. (2007) The release of substance P from cultured dorsal root ganglion neurons requires the non-neuronal cells around these neurons. Journal of Pharmacological Sciences 105, 264271.
Tucker, B.A., Rahimtula, M. and Mearow, K.M. (2005) A procedure for selecting and culturing subpopulations of neurons from rat dorsal root ganglia using magnetic beads. Brain Research Protocols 16, 5057.
Tucker, B.A., Rahimtula, M. and Mearow, K.M. (2006) Laminin and growth factor receptor activation stimulates differential growth responses in subpopulations of adult DRG neurons. European Journal of Neuroscience 24, 676690.
Vesce, S., Bezzi, P. and Volterra, A. (2001) Synaptic transmission with the glia. News Physiological Sciences 16, 178184.
Watkins, L.R., Hutchinson, M.R., Milligan, E.D. and Maier, S.F. (2007) “Listening” and “talking” to neurons: implications of immune activation for pain control and increasing the efficacy of opioids. Brain Research Reviews 56, 148169.
Wewetzer, K., Lausch, M. and Christ, B. (1999) Macrowell cultures identify a subpopulation of neonatal rat dorsal root ganglionic neurons displaying nerve growth factor independent survival. Neuroscience Letters 276, 912.
Wise, H. (2006) Lack of interaction between prostaglandin E2 receptor subtypes in regulating adenylyl cyclase activity in cultured rat dorsal root ganglion cells. European Journal of Pharmacology 535, 6977.
Wong, W.S.F. and Rosoff, P.M. (1996) Pharmacology of pertussis toxin B-oligomer. Canadian Journal of Physiology and Pharmacology 74, 559564.
Wu, D., Zhang, Y., Bo, X., Huang, W., Xiao, F., Zhang, X. et al. (2007) Actions of neuropoietic cytokines and cyclic AMP in regenerative conditioning of rat primary sensory neurons. Experimental Neurology 204, 6676.
Zhang, X., Chen, Y., Wang, C. and Huang, L.-Y.M. (2007) Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia. Proceedings of the National Academy of Sciences of the U.S.A. 104, 98649869.
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