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Sphingosine kinase 1 in murine dorsal root ganglia

1 Immunology and SA Pathology, Centre for Neuroscience, Flinders University, 5001 Adelaide, Australia;
2 Department of Physiology and Medical Physics, Division of Physiology, Innsbruck Medical University, 6020 Innsbruck, Austria;
3 Centre for Cancer Biology, University of South Australia and SA Pathology, 5000 Adelaide, Australia;
4 Anatomy & Histology, Centre for Neuroscience, Flinders University, 5001 Adelaide, Australia

Special Issues: Role of the bioactive sphingolipid, sphingosine-1-phosphate, in health and diseases

The bioactive sphingolipid, sphingosine 1-phosphate (S1P), is a multifunctional mediator that regulates a multitude of processes such as proliferation and differentiation, immune responses, airway constriction and nociception. S1P is synthesized by two sphingosine kinase isoforms, Sphk1 and Sphk2, which are expressed ubiquitously, but exhibit differential tissue expression patterns among organs. S1P has been shown to be involved in sensory neuron nociceptive signalling. However, the presence and regulation of Sphk expression in sensory neurons under conditions of persistent inflammatory pain are currently unknown. We therefore assessed the expression levels of Sphk in murine dorsal root ganglion (DRG) neurons, explored the localisation of Sphk mRNA using In-Situ-Hybridization and used mice with a global null mutation for Sphk1 to investigate the response of sensory neurons in a model of persistent inflammation. Here we showed the expression of both Sphk isoforms in mouse primary sensory neurons. The relative mRNA expression levels for markers of inflammation and nociceptive activity, TNFα and NPY, increased whereas mRNA expression levels for Sphk1 but not Sphk2 decreased in ipsilateral DRG in response to peripheral inflammation. Mice with a global deletion of Sphk1 showed a substantial reduction in Sphk1- but not Sphk2-activity in spinal cord but responded to CFA inflammation in a similar way to control mice, with increased sensitivity to mechanical and thermal stimuli, although the degree of inflammation-induced paw swelling was slightly increased in the Sphk1-/- mice. In summary, Sphk1 mRNA was expressed in virtually all sensory DRG neurons and its expression changed in response to peripheral inflammation. However, deficiency of Sphk1did not impact on the inflammation-dependent changes in the expression of pro-inflammatory markers in DRGs, nor did it significantly change nocifensive behaviour.
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Keywords Sphingosine 1-phosphate; mRNA; DRG; CFA; inflammation; Sphk1-/-; mouse; In-Situ-Hybridisation

Citation: Dimitra Beroukas, Maurice Selhorst, Stuart M. Pitson, Dusan Matusica, Ian L. Gibbins, Michaela Kress, Rainer V. Haberberger. Sphingosine kinase 1 in murine dorsal root ganglia. AIMS Molecular Science, 2015, 1(1): 22-33. doi: 10.3934/molsci.2015.1.22


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Copyright Info: 2015, Rainer V. Haberberger, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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