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Ependymal cells along the lateral ventricle express functional P2X7 receptors

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Abstract

Ependymal cells line the cerebral ventricles and are located in an ideal position to detect central nervous system injury and inflammation. The signaling mechanisms of ependymal cells, however, are poorly understood. As extracellular adenosine 5′-triphosphate is elevated in the context of cellular damage, experiments were conducted to determine whether ependymal cells along the mouse subventricular zone (SVZ) express functional purinergic receptors. Using whole-cell patch clamp recording, widespread expression of P2X7 receptors was detected on ependymal cells based on their antagonist sensitivity profile and absence of response in P2X7 −/− mice. Immunocytochemistry confirmed the expression of P2X7 receptors, and electron microscopy demonstrated that P2X7 receptors are expressed on both cilia and microvilli. Ca2+ imaging showed that P2X7 receptors expressed on cilia are indeed functional. As ependymal cells are believed to function as partner cells in the SVZ neurogenic niche, P2X7 receptors may play a role in neural progenitor response to injury and inflammation.

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Abbreviations

aCSF:

Artificial cerebrospinal fluid

BBG:

Brilliant blue G

BzATP:

2′(3′)-O-(4-benzoylbenzoyl)adenosine 5′-triphosphate triethylammonium salt

[Ca2+]i :

Intracellular Ca2+ concentration

DIC:

Differential interference contrast

GLAST:

Glutamate/aspartate transporter

MFA:

Meclofenamic acid

oATP:

Adenosine 5′-triphosphate-2′,3′-dialdehyde

PPADS:

Pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate

SVZ:

Subventricular zone

References

  1. Del Bigio MR (1995) The ependyma: a protective barrier between brain and cerebrospinal fluid. Glia 14:1–13. doi:10.1002/glia.440140102

    Article  PubMed  CAS  Google Scholar 

  2. Lim DA, Tramontin AD, Trevejo JM et al (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28:713–726. doi:10.1016/S0896-6273(00)00148-3

    Article  PubMed  CAS  Google Scholar 

  3. Ramírez-Castillejo C, Sánchez-Sánchez F, Andreu-Agulló C et al (2006) Pigment epithelium-derived factor is a niche signal for neural stem cell renewal. Nat Neurosci 9:331–339. doi:10.1038/nn1657

    Article  PubMed  CAS  Google Scholar 

  4. Genzen JR, Bordey A (2009) Ependymal cells and the neurogenic niche. In: Bonfanti L (ed) Postnatal and adult neurogenesis. Kerala, India, Research Signpost (in press)

  5. Ohlstein B, Kai T, Decotto E et al (2004) The stem cell niche: theme and variations. Curr Opin Cell Biol 16:693–699. doi:10.1016/j.ceb.2004.09.003

    Article  PubMed  CAS  Google Scholar 

  6. Sawamoto K, Wichterle H, Gonzalez-Perez O et al (2006) New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311:629–632. doi:10.1126/science.1119133

    Article  PubMed  CAS  Google Scholar 

  7. Franke H, Krugel U, Illes P (2006) P2 receptors and neuronal injury. Pflugers Arch 452:622–644. doi:10.1007/s00424-006-0071-8

    Article  PubMed  CAS  Google Scholar 

  8. Juranyi Z, Sperlagh B, Vizi ES (1999) Involvement of P2 purinoceptors and the nitric oxide pathway in [3H] purine outflow evoked by short-term hypoxia and hypoglycemia in rat hippocampal slices. Brain Res 823:183–190. doi:10.1016/S0006-8993(99)01169-5

    Article  PubMed  CAS  Google Scholar 

  9. Wallman-Johansson A, Fredholm BB (1994) Release of adenosine and other purines from hippocampal slices stimulated electrically or by hypoxia/hypoglycemia. Effect of chlormethiazole. Life Sci 55:721–728. doi:10.1016/0024-3205(94)00680-6

    Article  PubMed  CAS  Google Scholar 

  10. Cunha RA, Vizi ES, Ribeiro JA et al (1996) Preferential release of ATP and its extracellular catabolism as a source of adenosine upon high- but not low-frequency stimulation of rat hippocampal slices. J Neurochem 67:2180–2187

    Article  PubMed  CAS  Google Scholar 

  11. Franke H, Grummich B, Hartig W et al (2006) Changes in purinergic signaling after cerebral injury—involvement of glutamatergic mechanisms? Int J Dev Neurosci 24:123–132. doi:10.1016/j.ijdevneu.2005.11.016

    Article  PubMed  CAS  Google Scholar 

  12. Collo G, Neidhart S, Kawashima E et al (1997) Tissue distribution of the P2X7 receptor. Neuropharmacology 36:1277–1283. doi:10.1016/S0028-3908(97)00140-8

    Article  PubMed  CAS  Google Scholar 

  13. Yu Y, Ugawa S, Ueda T et al (2008) Cellular localization of P2X7 receptor mRNA in the rat brain. Brain Res 1194:45–55. doi:10.1016/j.brainres.2007.11.064

    Article  PubMed  CAS  Google Scholar 

  14. Sim JA, Young MT, Sung HY et al (2004) Reanalysis of P2X7 receptor expression in rodent brain. J Neurosci 24:6307–6314. doi:10.1523/JNEUROSCI.1469-04.2004

    Article  PubMed  CAS  Google Scholar 

  15. Surprenant A, Rassendren F, Kawashima E et al (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272:735–738. doi:10.1126/science.272.5262.735

    Article  PubMed  CAS  Google Scholar 

  16. Virginio C, Church D, North RA et al (1997) Effects of divalent cations, protons and calmidazolium at the rat P2X7 receptor. Neuropharmacology 36:1285–1294. doi:10.1016/S0028-3908(97)00141-X

    Article  PubMed  CAS  Google Scholar 

  17. Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25:5071–5082. doi:10.1038/sj.emboj.7601378

    Article  PubMed  CAS  Google Scholar 

  18. Anderson CM, Nedergaard M (2006) Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons. Trends Neurosci 29:257–262. doi:10.1016/j.tins.2006.03.003

    Article  PubMed  CAS  Google Scholar 

  19. Solle M, Labasi J, Perregaux DG et al (2001) Altered cytokine production in mice lacking P2X(7) receptors. J Biol Chem 276:125–132. doi:10.1074/jbc.M006781200

    Article  PubMed  CAS  Google Scholar 

  20. Liu X, Bolteus A, Balkin D et al (2006) GFAP-expressing progenitors in mouse postnatal subventricular zone display a unique glial phenotype intermediate between radial glia and astrocytes. Glia 54:394–410. doi:10.1002/glia.20392

    Article  PubMed  Google Scholar 

  21. Rubio ME (2006) Redistribution of synaptic AMPA receptors at glutamatergic synapses in the dorsal cochlear nucleus as an early response to cochlear ablation in rats. Hear Res 216–217:154–167. doi:10.1016/j.heares.2006.03.007

    Article  PubMed  CAS  Google Scholar 

  22. Platel JC, Dupuis A, Boisseau S et al (2007) Synchrony of spontaneous calcium activity in mouse neocortex before synaptogenesis. Eur J Neurosci 25:920–928. doi:10.1111/j.1460-9568.2007.05367.x

    Article  PubMed  Google Scholar 

  23. Nguyen T, Chin WC, O’Brien JA et al (2001) Intracellular pathways regulating ciliary beating of rat brain ependymal cells. J Physiol 531:131–140. doi:10.1111/j.1469-7793.2001.0131j.x

    Article  PubMed  CAS  Google Scholar 

  24. Ma W, Korngreen A, Weil S et al (2006) Pore properties and pharmacological features of the P2X receptor channel in airway ciliated cells. J Physiol 571:503–517. doi:10.1113/jphysiol.2005.103408

    Article  PubMed  CAS  Google Scholar 

  25. Platel JC, Lacar B, Bordey A (2007) GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis. J Mol Histol 38:602–610

    PubMed  Google Scholar 

  26. Luo J, Shook BA, Daniels SB et al (2008) Subventricular zone-mediated ependyma repair in the adult mammalian brain. J Neurosci 28:3804–3813. doi:10.1523/JNEUROSCI.0224-08.2008

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Daniel Balkin as well as Jackson Laboratories for primer design. This work was supported by grants from the National Institute of Health R01 NS048256 and DC007681 (A.B.) and 2T32HL007974-05 (J.R.G.).

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Authors and Affiliations

  1. Department of Laboratory Medicine, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208035, New Haven, CT, 06520-8035, USA

    Jonathan R. Genzen

  2. Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, FMB 422, New Haven, CT, 06520-8082, USA

    Jean-Claude Platel & Angelique Bordey

  3. Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, FMB 422, New Haven, CT, 06520-8082, USA

    Jean-Claude Platel & Angelique Bordey

  4. Department of Physiology and Neurobiology, University of Connecticut, TLS 102B, 75 North Eagleville Road, Unit 3156, Storrs, CT, 06269-3156, USA

    Maria E. Rubio

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  1. Jonathan R. Genzen
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  2. Jean-Claude Platel
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  3. Maria E. Rubio
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  4. Angelique Bordey
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Correspondence to Angelique Bordey.

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Genzen, J.R., Platel, JC., Rubio, M.E. et al. Ependymal cells along the lateral ventricle express functional P2X7 receptors. Purinergic Signalling 5, 299–307 (2009). https://doi.org/10.1007/s11302-009-9143-5

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  • DOI: https://doi.org/10.1007/s11302-009-9143-5

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