Sphingosine kinase 1 in murine dorsal root ganglia

Dimitra Beroukas; Maurice Selhorst; Stuart M. Pitson; Dusan Matusica; Ian L. Gibbins; Michaela Kress; Rainer V. Haberberger; Dimitra Beroukas; Maurice Selhorst; Stuart M. Pitson; Dusan Matusica; Ian L. Gibbins; Michaela Kress; Rainer V. Haberberger

doi:10.3934/molsci.2015.1.22

AIMS Molecular Science

2015, Volume 1, Issue 1: 22-33. doi: 10.3934/molsci.2015.1.22

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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

Received: 11 August 2014 Accepted: 31 January 2015 Published: 08 February 2015

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.
- 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[J]. AIMS Molecular Science, 2015, 1(1): 22-33. doi: 10.3934/molsci.2015.1.22

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Abstract

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.

References

[1]	Maceyka M, Harikumar KB, Milstien S, et al. (2012) Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol 22: 50-60. doi: 10.1016/j.tcb.2011.09.003
[2]	Pitson SM (2011) Regulation of sphingosine kinase and sphingolipid signaling. Trends Biochem Sci 36: 97-107. doi: 10.1016/j.tibs.2010.08.001
[3]	Mizugishi K, Yamashita T, Olivera A, et al. (2005) Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol 25: 11113-11121. doi: 10.1128/MCB.25.24.11113-11121.2005
[4]	Chan H, Pitson SM (2013) Post-translational regulation of sphingosine kinases. Biochim Biophys Acta 1831: 147-156. doi: 10.1016/j.bbalip.2012.07.005
[5]	Baker DA, Barth J, Chang R, et al. (2010) Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis. J Immunol 185: 2570-2579. doi: 10.4049/jimmunol.1000644
[6]	Toman RE, Payne SG, Watterson KR, et al. (2004) Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension. J Cell Biol 166: 381-392. doi: 10.1083/jcb.200402016
[7]	Zhang YH, Vasko MR, Nicol GD (2006) Intracellular sphingosine 1-phosphate mediates the increased excitability produced by nerve growth factor in rat sensory neurons. J Physiol 575: 101-113. doi: 10.1113/jphysiol.2006.111575
[8]	Zhang YH, Fehrenbacher JC, Vasko MR, et al. (2006) Sphingosine-1-phosphate via activation of a G-protein-coupled receptor(s) enhances the excitability of rat sensory neurons. J Neurophysiol 96: 1042-1052. doi: 10.1152/jn.00120.2006
[9]	He XH, Zang Y, Chen X, et al. (2010) TNF-alpha contributes to up-regulation of Nav1.3 and Nav1.8 in DRG neurons following motor fiber injury. Pain 151: 266-279.
[10]	Hokfelt T, Brumovsky P, Shi T, et al. (2007) NPY and pain as seen from the histochemical side. Peptides 28: 365-372. doi: 10.1016/j.peptides.2006.07.024
[11]	Mair N, Benetti C, Andratsch M, et al. (2011) Genetic evidence for involvement of neuronally expressed S1P(1) receptor in nociceptor sensitization and inflammatory pain. PLoS One 6: e17268. doi: 10.1371/journal.pone.0017268
[12]	Camprubi-Robles M, Mair N, Andratsch M, et al. (2013) Sphingosine-1-phosphate-induced nociceptor excitation and ongoing pain behavior in mice and humans is largely mediated by S1P3 receptor. J Neurosci 33: 2582-2592. doi: 10.1523/JNEUROSCI.4479-12.2013
[13]	Salvemini D, Doyle T, Kress M, et al. (2013) Therapeutic targeting of the ceramide-to-sphingosine 1-phosphate pathway in pain. Trends Pharmacol Sci 34: 110-118. doi: 10.1016/j.tips.2012.12.001
[14]	Allende ML, Sasaki T, Kawai H, et al. (2004) Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. J Biol Chem 279: 52487-52492. doi: 10.1074/jbc.M406512200
[15]	Pitman MR, Pham DH, Pitson SM (2012) Isoform-selective assays for sphingosine kinase activity. Methods Mol Biol 874: 21-31. doi: 10.1007/978-1-61779-800-9_2
[16]	Hargreaves K, Dubner R, Brown F, et al. (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32: 77-88. doi: 10.1016/0304-3959(88)90026-7
[17]	Xie W, Strong JA, Kays J, et al. (2012) Knockdown of the sphingosine-1-phosphate receptor S1PR1 reduces pain behaviors induced by local inflammation of the rat sensory ganglion. Neurosci Lett 515: 61-65. doi: 10.1016/j.neulet.2012.03.019
[18]	Coste O, Pierre S, Marian C, et al. (2008) Antinociceptive activity of the S1P-receptor agonist FTY720. J Cell Mol Med 12: 995-1004. doi: 10.1111/j.1582-4934.2008.00160.x
[19]	Meng H, Yuan Y, Lee VM (2011) Loss of sphingosine kinase 1/S1P signaling impairs cell growth and survival of neurons and progenitor cells in the developing sensory ganglia. PLoS One 6: e27150. doi: 10.1371/journal.pone.0027150
[20]	Pollock J, McFarlane SM, Connell MC, et al. (2002) TNF-alpha receptors simultaneously activate Ca2+ mobilisation and stress kinases in cultured sensory neurones. Neuropharmacology 42: 93-106. doi: 10.1016/S0028-3908(01)00163-0
[21]	Nicol GD (2008) Nerve growth factor, sphingomyelins, and sensitization in sensory neurons. Sheng Li Xue Bao 60: 603-604.
[22]	Blondeau N, Lai Y, Tyndall S, et al. (2007) Distribution of sphingosine kinase activity and mRNA in rodent brain. J Neurochem 103: 509-517. doi: 10.1111/j.1471-4159.2007.04755.x
[23]	Li Y, Ji A, Weihe E, et al. (2004) Cell-specific expression and lipopolysaccharide-induced regulation of tumor necrosis factor alpha (TNFalpha) and TNF receptors in rat dorsal root ganglion. J Neurosci 24: 9623-9631. doi: 10.1523/JNEUROSCI.2392-04.2004
[24]	Ji RR, Zhang X, Wiesenfeld-Hallin Z, et al. (1994) Expression of neuropeptide Y and neuropeptide Y (Y1) receptor mRNA in rat spinal cord and dorsal root ganglia following peripheral tissue inflammation. J Neurosci 14: 6423-6434.
[25]	Kubicek L, Kopacik R, Klusakova I, et al. (2010) Alterations in the vascular architecture of the dorsal root ganglia in a rat neuropathic pain model. Ann Anat 192: 101-106. doi: 10.1016/j.aanat.2010.01.005
[26]	Nayak D, Huo Y, Kwang WX, et al. (2010) Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia. Neuroscience 166: 132-144. doi: 10.1016/j.neuroscience.2009.12.020
[27]	Grin'kina NM, Karnabi EE, Damania D, et al. (2012) Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation. PLoS One 7: e36475. doi: 10.1371/journal.pone.0036475
[28]	Michaud J, Kohno M, Proia RL, et al. (2006) Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice. FEBS Lett 580: 4607-4612. doi: 10.1016/j.febslet.2006.07.035

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