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Purine Signaling and Microglial Wrapping

  • Bernardo CastellanoEmail author
  • Mar Bosch-Queralt
  • Beatriz Almolda
  • Nàdia Villacampa
  • Berta González
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 949)

Abstract

Microglial cells are highly dynamic cells with processes continuously moving to survey the surrounding territory. Microglia possess a broad variety of surface receptors and subtle changes in their microenvironment cause microglial cell processes to extend, retract, and interact with neuronal synaptic contacts. When the nervous system is disturbed, microglia activate, proliferate, and migrate to sites of injury in response to alert signals. Released nucleotides like ATP and UTP are among the wide range of molecules promoting microglial activation and guiding their migration and phagocytic function. The increased concentration of nucleotides in the extracellular space could be involved in the microglial wrapping found around injured neurons in various pathological conditions, especially after peripheral axotomy. Microglial wrappings isolate injured neurons from synaptic inputs and facilitate the molecular dialog between endangered or injured neurons and activated microglia. Astrocytes may also participate in neuronal ensheathment. Degradation of ATP by microglial ecto-nucleotidases and the expression of various purine receptors might be decisive in regulating the function of enwrapping glial cells and in determining the fate of damaged neurons, which may die or may regenerate their axons and survive.

Keywords

ATP Adenosine CD39 ‘Eat-me’ signals Neuronal degeneration Nerve injury Microglial migration Phagocytosis Purine receptors Axotomy 

Abbreviations

CNS

Central nervous system

PAMPs

Pathogen associated molecular patterns

DAMPs

Damage associated molecular patterns

TLRs

Toll-like receptors

SAMPs

Self-associated molecular patterns

TREM2

Triggering Receptor Expressed on Myeloid cells 2

PPT

Perforant path transection

ECM

Extracellular matrix

Notes

Acknowledgments

This work was supported by the Spanish Ministry of Science and Innovation BFU2011-27400 and BFU2014-55459-P.

References

  1. Almolda B, Costa M, Montoya M, Gonzalez B, Castellano B (2009) CD4 microglial expression correlates with spontaneous clinical improvement in the acute Lewis rat EAE model. J Neuroimmunol 209(1–2):65–80. doi: 10.1016/j.jneuroim.2009.01.026 S0165-5728(09)00031-9 [pii]PubMedCrossRefGoogle Scholar
  2. Almolda B, Villacampa N, Manders P, Hidalgo J, Campbell IL, Gonzalez B, Castellano B (2014) Effects of astrocyte-targeted production of interleukin-6 in the mouse on the host response to nerve injury. Glia 62(7):1142–1161. doi: 10.1002/glia.22668 PubMedCrossRefGoogle Scholar
  3. Arbat-Plana A, Torres-Espin A, Navarro X, Udina E (2015) Activity dependent therapies modulate the spinal changes that motoneurons suffer after a peripheral nerve injury. Exp Neurol 263:293–305. doi: 10.1016/j.expneurol.2014.10.009 S0014-4886(14)00345-8 [pii]PubMedCrossRefGoogle Scholar
  4. Arbeloa J, Perez-Samartin A, Gottlieb M, Matute C (2012) P2X7 receptor blockade prevents ATP excitotoxicity in neurons and reduces brain damage after ischemia. Neurobiol Dis 45(3):954–961. doi: 10.1016/j.nbd.2011.12.014 S0969-9961(11)00389-5 [pii]PubMedCrossRefGoogle Scholar
  5. Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81(1):1–5. doi: 10.1189/jlb.0306164 jlb.0306164 [pii]PubMedCrossRefGoogle Scholar
  6. Biber K, Neumann H, Inoue K, Boddeke HW (2007) Neuronal ‘On’ and ‘Off’ signals control microglia. Trends Neurosci 30(11):596–602. doi: 10.1016/j.tins.2007.08.007 S0166-2236(07)00248-2 [pii]PubMedCrossRefGoogle Scholar
  7. Blinzinger K, Kreutzberg G (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z Zellforsch Mikrosk Anat 85(2):145–157PubMedCrossRefGoogle Scholar
  8. Borke RC, Bridwell RS, Nau ME (1995) The progression of deafferentation as a retrograde reaction to hypoglossal nerve injury. J Neurocytol 24(10):763–774PubMedCrossRefGoogle Scholar
  9. Braun N, Zhu Y, Krieglstein J, Culmsee C, Zimmermann H (1998) Upregulation of the enzyme chain hydrolyzing extracellular ATP after transient forebrain ischemia in the rat. J Neurosci 18(13):4891–4900PubMedGoogle Scholar
  10. Braun N, Sevigny J, Robson SC, Enjyoji K, Guckelberger O, Hammer K, Di Virgilio F, Zimmermann H (2000) Assignment of ecto-nucleoside triphosphate diphosphohydrolase-1/cd39 expression to microglia and vasculature of the brain. Eur J Neurosci 12(12):4357–4366 doi:ejn1342 [pii]PubMedGoogle Scholar
  11. Bulavina L, Szulzewsky F, Rocha A, Krabbe G, Robson SC, Matyash V, Kettenmann H (2013) NTPDase1 activity attenuates microglial phagocytosis. Purinergic Signal 9(2):199–205. doi: 10.1007/s11302-012-9339-y PubMedCrossRefGoogle Scholar
  12. Butt AM (2011) ATP: a ubiquitous gliotransmitter integrating neuron-glial networks. Semin Cell Dev Biol 22(2):205–213. doi: 10.1016/j.semcdb.2011.02.023 S1084-9521(11)00036-X [pii]PubMedCrossRefGoogle Scholar
  13. Cartier L, Hartley O, Dubois-Dauphin M, Krause KH (2005) Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases. Brain Res Brain Res Rev 48(1):16–42. doi: 10.1016/j.brainresrev.2004.07.021 S0165-0173(04)00116-X [pii]PubMedCrossRefGoogle Scholar
  14. Chen JL, Villa KL, Cha JW, So PT, Kubota Y, Nedivi E (2012) Clustered dynamics of inhibitory synapses and dendritic spines in the adult neocortex. Neuron 74(2):361–373. doi: 10.1016/j.neuron.2012.02.030 S0896-6273(12)00267-X [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chen Z, Jalabi W, Hu W, Park HJ, Gale JT, Kidd GJ, Bernatowicz R, Gossman ZC, Chen JT, Dutta R, Trapp BD (2014) Microglial displacement of inhibitory synapses provides neuroprotection in the adult brain. Nat Commun 5:4486. doi: 10.1038/ncomms5486 ncomms5486 [pii]PubMedPubMedCentralGoogle Scholar
  16. Chertoff M, Shrivastava K, Gonzalez B, Acarin L, Gimenez-Llort L (2013) Differential modulation of TREM2 protein during postnatal brain development in mice. PLoS One 8(8):e72083. doi: 10.1371/journal.pone.0072083 PONE-D-13-15299 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  17. Chung WS, Clarke LE, Wang GX, Stafford BK, Sher A, Chakraborty C, Joung J, Foo LC, Thompson A, Chen C, Smith SJ, Barres BA (2013) Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 504(7480):394–400. doi: 10.1038/nature12776 nature12776 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  18. Cisneros-Mejorado A, Perez-Samartin A, Gottlieb M, Matute C (2015) ATP signaling in brain: release, excitotoxicity and potential therapeutic targets. Cell Mol Neurobiol 35(1):1–6. doi: 10.1007/s10571-014-0092-3 PubMedCrossRefGoogle Scholar
  19. Dalmau I, Vela JM, Gonzalez B, Castellano B (1998) Expression of purine metabolism-related enzymes by microglial cells in the developing rat brain. J Comp Neurol 398(3):333–346. doi: 10.1002/(SICI)1096-9861(19980831)398:3<333:AID-CNE3>3.0.CO;2-0 [pii]PubMedCrossRefGoogle Scholar
  20. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8(6):752–758. doi: 10.1038/nn1472 nn1472 [pii]PubMedCrossRefGoogle Scholar
  21. de Jong EK, Dijkstra IM, Hensens M, Brouwer N, van Amerongen M, Liem RS, Boddeke HW, Biber K (2005) Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible explanation for microglia activation remote from a primary lesion. J Neurosci 25(33):7548–7557. doi: 10.1523/JNEUROSCI.1019-05.2005 25/33/7548 [pii]PubMedCrossRefGoogle Scholar
  22. Eyo UB, Wu LJ (2013) Bidirectional microglia-neuron communication in the healthy brain. Neural Plast 2013:456857. doi: 10.1155/2013/456857 PubMedPubMedCentralGoogle Scholar
  23. Fang KM, Yang CS, Sun SH, Tzeng SF (2009) Microglial phagocytosis attenuated by short-term exposure to exogenous ATP through P2X receptor action. J Neurochem 111(5):1225–1237. doi: 10.1111/j.1471-4159.2009.06409.x JNC6409 [pii]PubMedCrossRefGoogle Scholar
  24. Farber K, Pannasch U, Kettenmann H (2005) Dopamine and noradrenaline control distinct functions in rodent microglial cells. Mol Cell Neurosci 29(1):128–138. doi: 10.1016/j.mcn.2005.01.003 S1044-7431(05)00010-2 [pii]PubMedCrossRefGoogle Scholar
  25. Farber K, Markworth S, Pannasch U, Nolte C, Prinz V, Kronenberg G, Gertz K, Endres M, Bechmann I, Enjyoji K, Robson SC, Kettenmann H (2008) The ectonucleotidase cd39/ENTPDase1 modulates purinergic-mediated microglial migration. Glia 56(3):331–341. doi: 10.1002/glia.20606 PubMedCrossRefGoogle Scholar
  26. Fleisher-Berkovich S, Filipovich-Rimon T, Ben-Shmuel S, Hulsmann C, Kummer MP, Heneka MT (2010) Distinct modulation of microglial amyloid beta phagocytosis and migration by neuropeptides (i). J Neuroinflammation 7:61. doi: 10.1186/1742-2094-7-61 1742-2094-7-61 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  27. Fontainhas AM, Wang M, Liang KJ, Chen S, Mettu P, Damani M, Fariss RN, Li W, Wong WT (2011) Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission. PLoS One 6(1):e15973. doi: 10.1371/journal.pone.0015973 PubMedPubMedCentralCrossRefGoogle Scholar
  28. Gehrmann J, Monaco S, Kreutzberg GW (1991) Spinal cord microglial cells and DRG satellite cells rapidly respond to transection of the rat sciatic nerve. Restor Neurol Neurosci 2(4):181–198. doi: 10.3233/RNN-1991-245605 F2852H884540843H [pii]PubMedGoogle Scholar
  29. Gonzalez H, Elgueta D, Montoya A, Pacheco R (2014) Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. J Neuroimmunol 274(1–2):1–13. doi: 10.1016/j.jneuroim.2014.07.012 S0165-5728(14)00227-6 [pii]PubMedCrossRefGoogle Scholar
  30. Hao HP, Doh-Ura K, Nakanishi H (2007) Impairment of microglial responses to facial nerve axotomy in cathepsin S-deficient mice. J Neurosci Res 85(10):2196–2206. doi: 10.1002/jnr.21357 PubMedCrossRefGoogle Scholar
  31. Hardingham GE, Bading H (2003) The Yin and Yang of NMDA receptor signalling. Trends Neurosci 26(2):81–89. doi: 10.1016/S0166-2236(02)00040-1 S0166-2236(02)00040-1 [pii]PubMedCrossRefGoogle Scholar
  32. Hardingham GE, Fukunaga Y, Bading H (2002) Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 5(5):405–414. doi: 10.1038/nn835 [pii]PubMedGoogle Scholar
  33. Hasko G, Pacher P, Deitch EA, Vizi ES (2007) Shaping of monocyte and macrophage function by adenosine receptors. Pharmacol Ther 113(2):264–275. doi: 10.1016/j.pharmthera.2006.08.003 S0163-7258(06)00150-1 [pii]PubMedCrossRefGoogle Scholar
  34. Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, Julius D (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9(12):1512–1519. doi: 10.1038/nn1805 nn1805 [pii]PubMedCrossRefGoogle Scholar
  35. Heine C, Heimrich B, Vogt J, Wegner A, Illes P, Franke H (2006) P2 receptor-stimulation influences axonal outgrowth in the developing hippocampus in vitro. Neuroscience 138(1):303–311. doi: 10.1016/j.neuroscience.2005.11.056 S0306-4522(05)01295-9 [pii]PubMedCrossRefGoogle Scholar
  36. Hirrlinger J, Hulsmann S, Kirchhoff F (2004) Astroglial processes show spontaneous motility at active synaptic terminals in situ. Eur J Neurosci 20(8):2235–2239. doi: 10.1111/j.1460-9568.2004.03689.x EJN3689 [pii]PubMedCrossRefGoogle Scholar
  37. Holtmaat A, De Paola V, Wilbrecht L, Knott GW (2008) Imaging of experience-dependent structural plasticity in the mouse neocortex in vivo. Behav Brain Res 192(1):20–25. doi: 10.1016/j.bbr.2008.04.005 S0166-4328(08)00190-3 [pii]PubMedCrossRefGoogle Scholar
  38. Husemann J, Loike JD, Anankov R, Febbraio M, Silverstein SC (2002) Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia 40(2):195–205. doi: 10.1002/glia.10148 PubMedCrossRefGoogle Scholar
  39. Ifuku M, Farber K, Okuno Y, Yamakawa Y, Miyamoto T, Nolte C, Merrino VF, Kita S, Iwamoto T, Komuro I, Wang B, Cheung G, Ishikawa E, Ooboshi H, Bader M, Wada K, Kettenmann H, Noda M (2007) Bradykinin-induced microglial migration mediated by B1-bradykinin receptors depends on Ca2+ influx via reverse-mode activity of the Na+/Ca2+ exchanger. J Neurosci 27(48):13065–13073. doi: 10.1523/JNEUROSCI.3467-07.2007 27/48/13065 [pii]PubMedCrossRefGoogle Scholar
  40. Ifuku M, Okuno Y, Yamakawa Y, Izumi K, Seifert S, Kettenmann H, Noda M (2011) Functional importance of inositol-1,4,5-triphosphate-induced intracellular Ca2+ mobilization in galanin-induced microglial migration. J Neurochem 117(1):61–70. doi: 10.1111/j.1471-4159.2011.07176.x PubMedCrossRefGoogle Scholar
  41. Inoue K (2008) Purinergic systems in microglia. Cell Mol Life Sci 65(19):3074–3080. doi: 10.1007/s00018-008-8210-3 PubMedCrossRefGoogle Scholar
  42. Jensen MB, Gonzalez B, Castellano B, Zimmer J (1994) Microglial and astroglial reactions to anterograde axonal degeneration: a histochemical and immunocytochemical study of the adult rat fascia dentata after entorhinal perforant path lesions. Exp Brain Res 98(2):245–260PubMedCrossRefGoogle Scholar
  43. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91(2):461–553. doi: 10.1152/physrev.00011.2010 91/2/461 [pii]PubMedCrossRefGoogle Scholar
  44. Kettenmann H, Kirchhoff F, Verkhratsky A (2013) Microglia: new roles for the synaptic stripper. Neuron 77(1):10–18. doi: 10.1016/j.neuron.2012.12.023 S0896-6273(12)01162-2 [pii]PubMedCrossRefGoogle Scholar
  45. Kierdorf K, Prinz M (2013) Factors regulating microglia activation. Front Cell Neurosci 7:44. doi: 10.3389/fncel.2013.00044 PubMedPubMedCentralCrossRefGoogle Scholar
  46. Kiryu-Seo S, Kiyama H (2011) The nuclear events guiding successful nerve regeneration. Front Mol Neurosci 4:53. doi: 10.3389/fnmol.2011.00053 PubMedPubMedCentralCrossRefGoogle Scholar
  47. Kiryu-Seo S, Hirayama T, Kato R, Kiyama H (2005) Noxa is a critical mediator of p53-dependent motor neuron death after nerve injury in adult mouse. J Neurosci 25(6):1442–1447. doi: 10.1523/JNEUROSCI.4041-04.2005 25/6/1442 [pii]PubMedCrossRefGoogle Scholar
  48. Knott G, Holtmaat A (2008) Dendritic spine plasticity–current understanding from in vivo studies. Brain Res Rev 58(2):282–289. doi: 10.1016/j.brainresrev.2008.01.002 S0165-0173(08)00004-0 [pii]PubMedCrossRefGoogle Scholar
  49. Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S, Inoue K (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446(7139):1091–1095. doi: 10.1038/nature05704 nature05704 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  50. Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19(8):312–318. doi: 10.1016/0166-2236(96)10049-7 [pii]PubMedCrossRefGoogle Scholar
  51. Kurpius D, Nolley EP, Dailey ME (2007) Purines induce directed migration and rapid homing of microglia to injured pyramidal neurons in developing hippocampus. Glia 55(8):873–884. doi: 10.1002/glia.20509 PubMedCrossRefGoogle Scholar
  52. Le Feuvre RA, Brough D, Touzani O, Rothwell NJ (2003) Role of P2X7 receptors in ischemic and excitotoxic brain injury in vivo. J Cereb Blood Flow Metab 23(3):381–384PubMedCrossRefGoogle Scholar
  53. Lehnardt S (2010) Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia 58(3):253–263. doi: 10.1002/glia.20928 PubMedGoogle Scholar
  54. Linda H, Shupliakov O, Ornung G, Ottersen OP, Storm-Mathisen J, Risling M, Cullheim S (2000) Ultrastructural evidence for a preferential elimination of glutamate-immunoreactive synaptic terminals from spinal motoneurons after intramedullary axotomy. J Comp Neurol 425(1):10–23. doi: 10.1002/1096-9861(20000911)425:1<10:AID-CNE2>3.0.CO;2-# [pii]PubMedCrossRefGoogle Scholar
  55. Linnartz B, Neumann H (2013) Microglial activatory (immunoreceptor tyrosine-based activation motif)- and inhibitory (immunoreceptor tyrosine-based inhibition motif)-signaling receptors for recognition of the neuronal glycocalyx. Glia 61(1):37–46. doi: 10.1002/glia.22359 PubMedCrossRefGoogle Scholar
  56. Liu GJ, Nagarajah R, Banati RB, Bennett MR (2009) Glutamate induces directed chemotaxis of microglia. Eur J Neurosci 29(6):1108–1118. doi: 10.1111/j.1460-9568.2009.06659.x EJN6659 [pii]PubMedCrossRefGoogle Scholar
  57. Makwana M, Jones LL, Cuthill D, Heuer H, Bohatschek M, Hristova M, Friedrichsen S, Ormsby I, Bueringer D, Koppius A, Bauer K, Doetschman T, Raivich G (2007) Endogenous transforming growth factor beta 1 suppresses inflammation and promotes survival in adult CNS. J Neurosci 27(42):11201–11213. doi: 10.1523/JNEUROSCI.2255-07.2007 27/42/11201 [pii]PubMedCrossRefGoogle Scholar
  58. Marin-Teva JL, Cuadros MA, Martin-Oliva D, Navascues J (2011) Microglia and neuronal cell death. Neuron Glia Biol 7(1):25–40. doi: 10.1017/S1740925X12000014 S1740925X12000014 [pii]PubMedCrossRefGoogle Scholar
  59. Martin S, Dicou E, Vincent JP, Mazella J (2005) Neurotensin and the neurotensin receptor-3 in microglial cells. J Neurosci Res 81(3):322–326. doi: 10.1002/jnr.20477 PubMedCrossRefGoogle Scholar
  60. Masui K, Yamada E, Shimokawara T, Mishima K, Enomoto Y, Nakajima H, Yoshikawa T, Sakaki T, Ichijima K (2002) Expression of c-Jun N-terminal kinases after axotomy in the dorsal motor nucleus of the vagus nerve and the hypoglossal nucleus. Acta Neuropathol 104(2):123–129. doi: 10.1007/s00401-002-0519-7 PubMedCrossRefGoogle Scholar
  61. Matute C, Torre I, Perez-Cerda F, Perez-Samartin A, Alberdi E, Etxebarria E, Arranz AM, Ravid R, Rodriguez-Antiguedad A, Sanchez-Gomez M, Domercq M (2007) P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. J Neurosci 27(35):9525–9533. doi: 10.1523/JNEUROSCI.0579-07.2007 27/35/9525 [pii]PubMedCrossRefGoogle Scholar
  62. Matzinger P (2007) Friendly and dangerous signals: is the tissue in control? Nat Immunol 8(1):11–13. doi: 10.1038/ni0107-11 ni0107-11 [pii]PubMedCrossRefGoogle Scholar
  63. Mehta A, Prabhakar M, Kumar P, Deshmukh R, Sharma PL (2013) Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur J Pharmacol 698(1–3):6–18. doi: 10.1016/j.ejphar.2012.10.032 S0014-2999(12)00900-4 [pii]PubMedCrossRefGoogle Scholar
  64. Melani A, Turchi D, Vannucchi MG, Cipriani S, Gianfriddo M, Pedata F (2005) ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia. Neurochem Int 47(6):442–448. doi: 10.1016/j.neuint.2005.05.014 S0197-0186(05)00143-9 [pii]PubMedCrossRefGoogle Scholar
  65. Melchior B, Garcia AE, Hsiung BK, Lo KM, Doose JM, Thrash JC, Stalder AK, Staufenbiel M, Neumann H, Carson MJ (2010) Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer’s disease. ASN Neuro 2(3):e00037. doi: 10.1042/AN20100010 PubMedPubMedCentralCrossRefGoogle Scholar
  66. Mentis GZ, Greensmith L, Vrbova G (1993) Motoneurons destined to die are rescued by blocking N-methyl-D-aspartate receptors by MK-801. Neuroscience 54(2):283–285. doi: 10.1016/0306-4522(93)90253-C [pii]PubMedCrossRefGoogle Scholar
  67. Moran LB, Graeber MB (2004) The facial nerve axotomy model. Brain Res Brain Res Rev 44(2–3):154–178. doi: 10.1016/j.brainresrev.2003.11.004 S0165017303002595 [pii]PubMedCrossRefGoogle Scholar
  68. Mott RT, Ait-Ghezala G, Town T, Mori T, Vendrame M, Zeng J, Ehrhart J, Mullan M, Tan J (2004) Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production. Glia 46(4):369–379. doi: 10.1002/glia.20009 PubMedCrossRefGoogle Scholar
  69. Navarro X, Vivo M, Valero-Cabre A (2007) Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol 82(4):163–201. doi: 10.1016/j.pneurobio.2007.06.005 S0301-0082(07)00109-8 [pii]PubMedCrossRefGoogle Scholar
  70. Neumann J, Gunzer M, Gutzeit HO, Ullrich O, Reymann KG, Dinkel K (2006) Microglia provide neuroprotection after ischemia. FASEB J 20(6):714–716. doi: 10.1096/fj.05-4882fje 05-4882fje [pii]PubMedGoogle Scholar
  71. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314–1318. doi: 10.1126/science.1110647 1110647 [pii]PubMedCrossRefGoogle Scholar
  72. Noda M, Ifuku M, Mori Y, Verkhratsky A (2013) Calcium influx through reversed NCX controls migration of microglia. Adv Exp Med Biol 961:289–294. doi: 10.1007/978-1-4614-4756-6_24 PubMedCrossRefGoogle Scholar
  73. Ohsawa K, Kohsaka S (2011) Dynamic motility of microglia: purinergic modulation of microglial movement in the normal and pathological brain. Glia 59(12):1793–1799. doi: 10.1002/glia.21238 PubMedCrossRefGoogle Scholar
  74. Orr AG, Orr AL, Li XJ, Gross RE, Traynelis SF (2009) Adenosine A(2A) receptor mediates microglial process retraction. Nat Neurosci 12(7):872–878. doi: 10.1038/nn.2341 nn.2341 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  75. Panatier A, Robitaille R (2012) The soothing touch: microglial contact influences neuronal excitability. Dev Cell 23(6):1125–1126. doi: 10.1016/j.devcel.2012.11.015 S1534-5807(12)00535-7 [pii]PubMedCrossRefGoogle Scholar
  76. Perez-Alvarez A, Navarrete M, Covelo A, Martin ED, Araque A (2014) Structural and functional plasticity of astrocyte processes and dendritic spine interactions. J Neurosci 34(38):12738–12744. doi: 10.1523/JNEUROSCI.2401-14.2014 34/38/12738 [pii]PubMedCrossRefGoogle Scholar
  77. Perry VH, O’Connor V (2010) The role of microglia in synaptic stripping and synaptic degeneration: a revised perspective. ASN Neuro 2(5):e00047. doi: 10.1042/AN20100024 PubMedGoogle Scholar
  78. Pocock JM, Kettenmann H (2007) Neurotransmitter receptors on microglia. Trends Neurosci 30(10):527–535. doi: 10.1016/j.tins.2007.07.007 S0166-2236(07)00211-1 [pii]PubMedCrossRefGoogle Scholar
  79. Raivich G, Makwana M (2007) The making of successful axonal regeneration: genes, molecules and signal transduction pathways. Brain Res Rev 53(2):287–311. doi: 10.1016/j.brainresrev.2006.09.005 S0165-0173(06)00110-X [pii]PubMedCrossRefGoogle Scholar
  80. Rappert A, Bechmann I, Pivneva T, Mahlo J, Biber K, Nolte C, Kovac AD, Gerard C, Boddeke HW, Nitsch R, Kettenmann H (2004) CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion. J Neurosci 24(39):8500–8509. doi: 10.1523/JNEUROSCI.2451-04.2004 24/39/8500 [pii]PubMedCrossRefGoogle Scholar
  81. Raslan A, Ernst P, Werle M, Thieme H, Szameit K, Finkensieper M, Guntinas-Lichius O, Irintchev A (2014) Reduced cholinergic and glutamatergic synaptic input to regenerated motoneurons after facial nerve repair in rats: potential implications for recovery of motor function. Brain Struct Funct 219(3):891–909. doi: 10.1007/s00429-013-0542-6 PubMedCrossRefGoogle Scholar
  82. Rathbone MP, Middlemiss PJ, Gysbers JW, Andrew C, Herman MA, Reed JK, Ciccarelli R, Di Iorio P, Caciagli F (1999) Trophic effects of purines in neurons and glial cells. Prog Neurobiol 59(6):663–690. doi: 10.1016/S0301-0082(99)00017-9 [pii]PubMedCrossRefGoogle Scholar
  83. Ravichandran KS (2010) Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums. J Exp Med 207(9):1807–1817. doi: 10.1084/jem.20101157 jem.20101157 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  84. Sasaki Y, Hoshi M, Akazawa C, Nakamura Y, Tsuzuki H, Inoue K, Kohsaka S (2003) Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain. Glia 44(3):242–250. doi: 10.1002/glia.10293 PubMedCrossRefGoogle Scholar
  85. Siskova Z, Tremblay ME (2013) Microglia and synapse: interactions in health and neurodegeneration. Neural Plast 2013:425845. doi: 10.1155/2013/425845 PubMedPubMedCentralGoogle Scholar
  86. Sperlagh B, Illes P (2007) Purinergic modulation of microglial cell activation. Purinergic Signal 3(1–2):117–127. doi: 10.1007/s11302-006-9043-x PubMedCrossRefGoogle Scholar
  87. Stone TW (2002) Purines and neuroprotection. Adv Exp Med Biol 513:249–280PubMedCrossRefGoogle Scholar
  88. Sumner BE, Sutherland FI (1973) Quantitative electron microscopy on the injured hypoglossal nucleus in the rat. J Neurocytol 2(3):315–328PubMedCrossRefGoogle Scholar
  89. Takayama N, Ueda H (2005) Morphine-induced chemotaxis and brain-derived neurotrophic factor expression in microglia. J Neurosci 25(2):430–435. doi: 10.1523/JNEUROSCI.3170-04.2005 25/2/430 [pii]PubMedCrossRefGoogle Scholar
  90. Theodosis DT, Poulain DA, Oliet SH (2008) Activity-dependent structural and functional plasticity of astrocyte-neuron interactions. Physiol Rev 88(3):983–1008. doi: 10.1152/physrev.00036.2007 88/3/983 [pii]PubMedCrossRefGoogle Scholar
  91. Tozaki-Saitoh H, Tsuda M, Miyata H, Ueda K, Kohsaka S, Inoue K (2008) P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury. J Neurosci 28(19):4949–4956. doi: 10.1523/JNEUROSCI.0323-08.2008 28/19/4949 [pii]PubMedCrossRefGoogle Scholar
  92. Trapp BD, Wujek JR, Criste GA, Jalabi W, Yin X, Kidd GJ, Stohlman S, Ransohoff R (2007) Evidence for synaptic stripping by cortical microglia. Glia 55(4):360–368. doi: 10.1002/glia.20462 PubMedCrossRefGoogle Scholar
  93. Tremblay ME, Lowery RL, Majewska AK (2010) Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8(11):e1000527. doi: 10.1371/journal.pbio.1000527 PubMedPubMedCentralCrossRefGoogle Scholar
  94. Tyzack GE, Sitnikov S, Barson D, Adams-Carr KL, Lau NK, Kwok JC, Zhao C, Franklin RJ, Karadottir RT, Fawcett JW, Lakatos A (2014) Astrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression. Nat Commun 5:4294. doi: 10.1038/ncomms5294 ncomms5294 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  95. Villacampa N, Almolda B, Vilella A, Campbell IL, Gonzalez B, Castellano B (2015) Astrocyte-targeted production of IL-10 induces changes in microglial reactivity and reduces motor neuron death after facial nerve axotomy. Glia. doi: 10.1002/glia.22807 PubMedGoogle Scholar
  96. Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29(13):3974–3980. doi: 10.1523/JNEUROSCI.4363-08.2009 29/13/3974 [pii]PubMedCrossRefGoogle Scholar
  97. Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23(4):1398–1405 23/4/1398 [pii]PubMedGoogle Scholar
  98. Woo NH, Lu B (2006) Regulation of cortical interneurons by neurotrophins: from development to cognitive disorders. Neuroscientist 12(1):43–56. doi: 10.1177/1073858405284360 12/1/43 [pii]PubMedCrossRefGoogle Scholar
  99. Xie R, Villacampa N, Almolda B, González B, Castellano B, Campbell IL (2014) Interferon regulator factor (IRF) 8 regulates the microglial response to neuronal injury. Cytokine 70(1):77. doi: 10.1016/j.cyto.2014.07.209 CrossRefGoogle Scholar
  100. Xing C, Wang X, Cheng C, Montaner J, Mandeville E, Leung W, van Leyen K, Lok J, Lo EH (2014) Neuronal production of lipocalin-2 as a help-me signal for glial activation. Stroke 45(7):2085–2092. doi: 10.1161/STROKEAHA.114.005733 STROKEAHA.114.005733 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  101. Yamada J, Hayashi Y, Jinno S, Wu Z, Inoue K, Kohsaka S, Nakanishi H (2008) Reduced synaptic activity precedes synaptic stripping in vagal motoneurons after axotomy. Glia 56(13):1448–1462. doi: 10.1002/glia.20711 PubMedCrossRefGoogle Scholar
  102. Yamada J, Nakanishi H, Jinno S (2011) Differential involvement of perineuronal astrocytes and microglia in synaptic stripping after hypoglossal axotomy. Neuroscience 182:1–10. doi: 10.1016/j.neuroscience.2011.03.030 S0306-4522(11)00288-0 [pii]PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Bernardo Castellano
    • 1
    Email author
  • Mar Bosch-Queralt
    • 1
  • Beatriz Almolda
    • 1
  • Nàdia Villacampa
    • 1
  • Berta González
    • 1
  1. 1.Unit of Histology, Torre M5, Department of Cell Biology, Physiology and Immunology, Institute of NeurosciencesUniversitat Autònoma de BarcelonaBellaterraSpain

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