Skip to main content
SpringerLink
Log in

Multiple Actions of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Schwann Cell Biology

  • Chapter
  • First Online:
Pituitary Adenylate Cyclase Activating Polypeptide — PACAP

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 11))

Abstract

The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) is a well-recognized endogenously produced pleiotropic molecule that elicits a broad range of biological functions in various cell types, including in Schwann cells (SCs). Its main actions, which have been primarily associated to neuroprotection both in the central and peripheral nervous system (CNS and PNS), are currently being extended, and new intriguing roles in regulating several aspects of CNS and PNS physiology are emerging. The overall goal of the present chapteris to provide an update of the recent advances that have been made to elucidate the multiple actions elicited by PACAP in relationship to the complex biology of SCs, whose seminal role is to provide myelin ensheathment to nerve fibers forming peripheral nerves. After reviewing the main functions of this specific type of neuroglia, a major goal will be to describe PACAP regulatory roles in several biological processes in SCs, including myelin generation, cell protection against injury and its secretagogue activity on proteolytic enzymes. Furthermore, a discussion on the impact that PACAP-mediated changes may have on peripheral axonal myelination and repair processes after nerve injury will be opened. The final aim will be to illustrate the potential benefits of PACAP treatment in chronic pain. In this section, particular attention will be given to those findings inferring on SCs involvement in the development of neuropathic pain and the key modulatory role elicited by PACAP. The contents herein summarized could offer a new perspective of PACAP to aid in the future development of more stable peptide analogues in the scenario of peripheral neuropathies and provide a comprehensive tool that will help to dissect novel PACAP-regulated functions in SCs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, et al. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun. 1989;164:567–74.

    Article  CAS  PubMed  Google Scholar 

  2. Castorina A, Tiralongo A, Giunta S, Carnazza ML, Rasi G, D’Agata V. PACAP and VIP prevent apoptosis in schwannoma cells. Brain Res. 2008;1241:29–35.

    Article  CAS  PubMed  Google Scholar 

  3. Giunta S, Castorina A, Adorno A, Mazzone V, Carnazza ML, D'Agata V. PACAP and VIP affect NF1 expression in rat malignant peripheral nerve sheath tumor (MPNST) cells. Neuropeptides. 2010;44:45–51.

    Article  CAS  PubMed  Google Scholar 

  4. Castorina A, Giunta S, Scuderi S, D’Agata V. Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells. J Mol Neurosci. 2012;48:674–83.

    Article  CAS  PubMed  Google Scholar 

  5. Stumm R, Kolodziej A, Prinz V, Endres M, Wu DF, Höllt V. Pituitary adenylate cyclase-activating polypeptide is up-regulated in cortical pyramidal cells after focal ischemia and protects neurons from mild hypoxic/ischemic damage. J Neurochem. 2007;103:1666–81.

    Article  CAS  PubMed  Google Scholar 

  6. Nakajima E, Walkup RD, Fujii A, Shearer TR, Azuma M. Pituitary adenylate cyclase-activating peptide induces neurite outgrowth in cultured monkey trigeminal ganglion cells: involvement of receptor PAC1. Mol Vis. 2013;19:174–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Kidd GJ, Ohno N, Trapp BD. Biology of Schwann cells. In: Aminoff MJ, Boller FO, Swaab DF, editors. Handb Clin Neurol. Elsevier; 2013;115:55–79.

    Google Scholar 

  8. Monk KR, Feltri ML, Taveggia C. New insights on Schwann cell development. Glia. 2015;63:1376–93.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Griffin JW, Thompson WJ. Biology and pathology of nonmyelinating Schwann cells. Glia. 2008;56:1518–31.

    Article  PubMed  Google Scholar 

  10. Yamazaki S, Ema H, Karlsson G, Yamaguchi T, Miyoshi H, Shioda S, et al. Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell. 2011;147:1146–58.

    Article  CAS  PubMed  Google Scholar 

  11. Ko CP, Sugiura Y, Feng Z. The biology of perisynaptic (terminal) Schwann cells. In: Armati PJ, editor. The biology of Schwann cells. Cambridge: Cambridge University Press; 2007. p. 72–99.

    Chapter  Google Scholar 

  12. Zhou XF, Deng YS, Chie E, Xue Q, Zhong JH, McLachlan EM, et al. Satellite cell-derived nerve growth factor and neurotrophin-3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat. Eur J Neurosci. 1999;11:1711–22.

    Article  CAS  PubMed  Google Scholar 

  13. Schwyn RC. An autoradiographic study of satellite cells in autonomic ganglia. Am J Anat. 1967;121:727–40.

    Article  CAS  PubMed  Google Scholar 

  14. Arroyo EJ, Scherer S. The molecular organisation of myelinating Schwann cells. In: Armati PJ, editor. The biology of Schwann cells. Cambridge: Cambridge University Press; 2007. p. 37–54.

    Chapter  Google Scholar 

  15. Armati PJ, Pollard JD, Gatenby P. Rat and human Schwann cells in vitro can synthesize and express MHC molecules. Muscle Nerve. 1990;13:106–16.

    Article  CAS  PubMed  Google Scholar 

  16. Nagano S, Takeda M, Ma L, Soliven B. Cytokine-induced cell death in immortalized Schwann cells: roles of nitric oxide and cyclic AMP. J Neurochem. 2001;77:1486–95.

    Article  CAS  PubMed  Google Scholar 

  17. Irnich D, Burgstahler R, Bostock H, Grafe P. ATP affects both axons and Schwann cells of unmyelinated C fibres. Pain. 2001;92:343–50.

    Article  CAS  PubMed  Google Scholar 

  18. Armati PJ, Mathey EK. An update on Schwann cell biology—immunomodulation, neural regulation and other surprises. J Neurol Sci. 2013;333:68–72.

    Article  CAS  PubMed  Google Scholar 

  19. Miyata A, Jiang L, Dahl RD, Kitada C, Kubo K, Fujino M, et al. Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38). Biochem Biophys Res Commun. 1990;170:643–8.

    Article  CAS  PubMed  Google Scholar 

  20. Dickson L, Finlayson K. VPAC and PAC receptors: from ligands to function. Pharmacol Ther. 2009;121:294–316.

    Article  CAS  PubMed  Google Scholar 

  21. Lutz EM, Ronaldson E, Shaw P, Johnson MS, Holland PJ, Mitchell R. Characterization of novel splice variants of the PAC1 receptor in human neuroblastoma cells: consequences for signaling by VIP and PACAP. Mol Cell Neurosci. 2006;31:193–209.

    Article  CAS  PubMed  Google Scholar 

  22. Holighaus Y, Mustafa T, Eiden LE. PAC1hop, null and hip receptors mediate differential signaling through cyclic AMP and calcium leading to splice variant-specific gene induction in neural cells. Peptides. 2011;32:1647–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Blechman J, Levkowitz G. Alternative splicing of the pituitary adenylate cyclase-activating polypeptide receptor PAC1: mechanisms of fine tuning of brain activity. Front Endocrinol (Lausanne). 2013;4:55.

    CAS  Google Scholar 

  24. Lakk M, Szabó B, Völgyi B, Gábriel R, Dénes V. Development-related splicing regulates pituitary adenylate cyclase-activating polypeptide (PACAP) receptors in the retina. Invest Ophthalmol Vis Sci. 2012;53:7825–32.

    Article  PubMed  Google Scholar 

  25. Dénes V, Czotter N, Lakk M, Berta G, Gábriel R. PAC1-expressing structures of neural retina alter their PAC1 isoform splicing during postnatal development. Cell Tissue Res. 2014;355:279–88.

    Article  PubMed  Google Scholar 

  26. Li M, David C, Kikuta T, Somogyvari-Vigh A, Arimura A. Signaling cascades involved in neuroprotection by subpicomolar pituitary adenylate cyclase-activating polypeptide 38. J Mol Neurosci. 2005;27:91–105.

    Article  PubMed  Google Scholar 

  27. Botia B, Jolivel V, Burel D, Le Joncour V, Roy V, Naassila M, et al. Neuroprotective effects of PACAP against ethanol-induced toxicity in the developing rat cerebellum. Neurotox Res. 2011;19:423–34.

    Article  CAS  PubMed  Google Scholar 

  28. Jóźwiak-Bębenista M, Kowalczyk E, Nowak JZ. The cyclic AMP effects and neuroprotective activities of PACAP and VIP in cultured astrocytes and neurons exposed to oxygen-glucose deprivation. Pharmacol Rep. 2015;67:332–8.

    Article  PubMed  Google Scholar 

  29. Juhász T, Matta C, Katona É, Somogyi C, Takács R, Gergely P, et al. Pituitary adenylate cyclase activating polypeptide (PACAP) signalling exerts chondrogenesis promoting and protecting effects: implication of calcineurin as a downstream target. PLoS One. 2014;9:e91541.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Giunta S, Castorina A, Marzagalli R, Szychlinska MA, Pichler K, Mobasheri A, et al. Ameliorative effects of PACAP against cartilage degeneration. Morphological, immunohistochemical and biochemical evidence from in vivo and in vitro models of rat osteoarthritis. Int J Mol Sci. 2015;16:5922–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Castorina A, Giunta S, Mazzone V, Cardile V, D'Agata V. Effects of PACAP and VIP on hyperglycemia-induced proliferation in murine microvascular endothelial cells. Peptides. 2010;31:2276–83.

    Article  CAS  PubMed  Google Scholar 

  32. Scuderi S, D'Amico AG, Castorina A, Imbesi R, Carnazza ML, D’Agata V. Ameliorative effect of PACAP and VIP against increased permeability in a model of outer blood retinal barrier dysfunction. Peptides. 2013;39:119–24.

    Article  CAS  PubMed  Google Scholar 

  33. Giunta S, Castorina A, Bucolo C, Magro G, Drago F, D’Agata V. Early changes in pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide and related receptors expression in retina of streptozotocin-induced diabetic rats. Peptides. 2012;37:32–9.

    Article  CAS  PubMed  Google Scholar 

  34. Marzagalli R, Scuderi S, Drago F, Waschek JA, Castorina A. Emerging role of PACAP as a new potential therapeutic target in major diabetes complications. Int J Endocrinol. 2015;2015:160928.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Ji H, Zhang Y, Shen XD, Gao F, Huang CY, Abad C, et al. Neuropeptide PACAP in mouse liver ischemia and reperfusion injury: immunomodulation by the cAMP-PKA pathway. Hepatology. 2013;57:1225–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lee J, Park HJ, Choi HS, Kwon HB, Arimura A, Lee BJ, et al. Gonadotropin stimulation of pituitary adenylate cyclase-activating polypeptide (PACAP) messenger ribonucleic acid in the rat ovary and the role of PACAP as a follicle survival factor. Endocrinology. 1999;140:818–26.

    CAS  PubMed  Google Scholar 

  37. Waschek JA. VIP and PACAP: neuropeptide modulators of CNS inflammation, injury, and repair. Br J Pharmacol. 2013;169:512–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Reglodi D, Kiss P, Szabadfi K, Atlasz T, Gabriel R, Horvath G, et al. PACAP is an endogenous protective factor-insights from PACAP-deficient mice. J Mol Neurosci. 2012;48:482–92.

    Article  CAS  PubMed  Google Scholar 

  39. Shioda S, Ohtaki H, Nakamachi T, Dohi K, Watanabe J, Nakajo S, et al. Pleiotropic functions of PACAP in the CNS: neuroprotection and neurodevelopment. Ann N Y Acad Sci. 2006;1070:550–60.

    Article  CAS  PubMed  Google Scholar 

  40. Broca C, Quoyer J, Costes S, Linck N, Varrault A, Deffayet PM, et al. Beta-Arrestin 1 is required for PAC1 receptor-mediated potentiation of long-lasting ERK1/2 activation by glucose in pancreatic beta-cells. J Biol Chem. 2009;284:4332–42.

    Article  CAS  PubMed  Google Scholar 

  41. Moroo I, Tatsuno I, Uchida D, Tanaka T, Saito J, Saito Y, et al. Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates mitogen-activated protein kinase (MAPK) in cultured rat astrocytes. Brain Res. 1998;795:191–6.

    Article  CAS  PubMed  Google Scholar 

  42. Juhász T, Helgadottir SL, Tamás A, Reglődi D, Zákány R. PACAP and VIP signaling in chondrogenesis and osteogenesis. Peptides. 2015;66:51–7.

    Article  PubMed  Google Scholar 

  43. Izumi S, Seki T, Shioda S, Zhou CJ, Arimura A, Koide R. Ultrastructural localization of PACAP immunoreactivity in the rat retina. Ann N Y Acad Sci. 2000;921:317–20.

    Article  CAS  PubMed  Google Scholar 

  44. Muroi M, Shioda S, Yada T, Zhou CJ, Nakai Y, Nakajo S, et al. Distribution and ultrastructural localization of PACAP receptors in the rat pancreatic islets. Ann N Y Acad Sci. 1998;865:438–40.

    Article  CAS  PubMed  Google Scholar 

  45. Jesuraj NJ, Nguyen PK, Wood MD, Moore AM, Borschel GH, Mackinnon SE, et al. Differential gene expression in motor and sensory Schwann cells in the rat femoral nerve. J Neurosci Res. 2012;90:96–104.

    Article  CAS  PubMed  Google Scholar 

  46. Hai M, Muja N, DeVries GH, Quarles RH, Patel PI. Comparative analysis of Schwann cell lines as model systems for myelin gene transcription studies. J Neurosci Res. 2002;69:497–508.

    Article  CAS  PubMed  Google Scholar 

  47. Jessen KR, Mirsky R. The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci. 2005;6:671–82.

    Article  CAS  PubMed  Google Scholar 

  48. Tamas A, Reglodi D, Farkas O, Kovesdi E, Pal J, Povlishock JT, et al. Effect of PACAP in central and peripheral nerve injuries. Int J Mol Sci. 2012;13:8430–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang QL, Liu J, Lin PX, Webster HD. Local administration of vasoactive intestinal peptide after nerve transection accelerates early myelination and growth of regenerating axons. J Peripher Nerv Syst. 2002;7:118–27.

    Article  CAS  PubMed  Google Scholar 

  50. Armstrong BD, Abad C, Chhith S, Cheung-Lau G, Hajji OE, Nobuta H, et al. Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide. Neuroscience. 2008;151:63–73.

    Article  CAS  PubMed  Google Scholar 

  51. Garratt AN, Voiculescu O, Topilko P, Charnay P, Birchmeier C. A dual role of erbB2 in myelination and in expansion of the Schwann cell precursor pool. J Cell Biol. 2000;148:1035–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Michailov GV, Sereda MW, Brinkmann BG, Fischer TM, Haug B, Birchmeier C, et al. Axonal neuregulin-1 regulates myelin sheath thickness. Science. 2004;304:700–3.

    Article  CAS  PubMed  Google Scholar 

  53. Taveggia C, Zanazzi G, Petrylak A, Yano H, Rosenbluth J, Einheber S, et al. Neuregulin-1 type III determines the ensheathment fate of axons. Neuron. 2005;47:681–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cheng L, Esch FS, Marchionni MA, Mudge AW. Control of Schwann cell survival and proliferation: autocrine factors and neuregulins. Mol Cell Neurosci. 1998;12:141–56.

    Article  CAS  PubMed  Google Scholar 

  55. Syroid DE, Maycox PR, Burrola PG, Liu N, Wen D, Lee KF, et al. Cell death in the Schwann cell lineage and its regulation by neuregulin. Proc Natl Acad Sci U S A. 1996;93:9229–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Castorina A, Scuderi S, D’Amico AG, Drago F, D’Agata V. PACAP and VIP increase the expression of myelin-related proteins in rat schwannoma cells: involvement of PAC1/VPAC2 receptor-mediated activation of PI3K/Akt signaling pathways. Exp Cell Res. 2014;322:108–21.

    Article  CAS  PubMed  Google Scholar 

  57. Vincze A, Reglodi D, Helyes Z, Hashimoto H, Shintani N, Abrahám H. Role of endogenous pituitary adenylate cyclase activating polypeptide (PACAP) in myelination of the rodent brain: lessons from PACAP-deficient mice. Int J Dev Neurosci. 2011;29:923–35.

    Article  CAS  PubMed  Google Scholar 

  58. Bansal R, Pfeiffer SE. Regulated galactolipid synthesis and cell surface expression in Schwann cell line D6P2T. J Neurochem. 1987;49:1902–11.

    Article  CAS  PubMed  Google Scholar 

  59. Lee M, Lelievre V, Zhao P, Torres M, Rodriguez W, Byun JY, et al. Pituitary adenylyl cyclase-activating polypeptide stimulates DNA synthesis but delays maturation of oligodendrocyte progenitors. J Neurosci. 2001;21:3849–59.

    CAS  PubMed  Google Scholar 

  60. Lelievre V, Ghiani CA, Seksenyan A, Gressens P, de Vellis J, Waschek JA. Growth factor-dependent actions of PACAP on oligodendrocyte progenitor proliferation. Regul Pept. 2006;137:58–66.

    Article  CAS  PubMed  Google Scholar 

  61. Ratner N, Miller SJ. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nat Rev Cancer. 2015;15:290–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Eccleston PA. Regulation of Schwann cell proliferation: mechanisms involved in peripheral nerve development. Exp Cell Res. 1992;199:1–9.

    Article  CAS  PubMed  Google Scholar 

  63. Uhlmann EJ, Gutmann DH. Tumor suppressor gene regulation of cell growth: recent insights into neurofibromatosis 1 and 2 gene function. Cell Biochem Biophys. 2001;34:61–78.

    Article  CAS  PubMed  Google Scholar 

  64. Shapira S, Barkan B, Friedman E, Kloog Y, Stein R. The tumor suppressor neurofibromin confers sensitivity to apoptosis by Ras-dependent and Ras-independent pathways. Cell Death Differ. 2007;14:895–906.

    CAS  PubMed  Google Scholar 

  65. Zusev M, Gozes I. Differential regulation of activity-dependent neuroprotective protein in rat astrocytes by VIP and PACAP. Regul Pept. 2004;123:33–41.

    Article  CAS  PubMed  Google Scholar 

  66. Nakamachi T, Li M, Shioda S, Arimura A. Signaling involved in pituitary adenylate cyclase-activating polypeptide-stimulated ADNP expression. Peptides. 2006;27:1859–64.

    Article  CAS  PubMed  Google Scholar 

  67. Masmoudi O, Gandolfo P, Leprince J, Vaudry D, Fournier A, Patte-Mensah C, et al. Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates endozepine release from cultured rat astrocytes via a PKA-dependent mechanism. FASEB J. 2003;17:17–27.

    Article  CAS  PubMed  Google Scholar 

  68. Masmoudi-Kouki O, Gandolfo P, Leprince J, Vaudry D, Pelletier G, Fournier A, et al. PACAP stimulates biosynthesis and release of endozepines from rat astrocytes. Ann N Y Acad Sci. 2006;1070:411–6.

    Article  CAS  PubMed  Google Scholar 

  69. Castorina A, Waschek JA, Marzagalli R, Cardile V, Drago F. PACAP interacts with PAC1 receptors to induce tissue plasminogen activator (tPA) expression and activity in Schwann cell-like cultures. PLoS One. 2015;10:e0117799.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Andero R, Ressler KJ. Fear extinction and BDNF: translating animal models of PTSD to the clinic. Genes Brain Behav. 2012;11:503–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pettersson LM, Geremia NM, Ying Z, Verge VM. Injury-associated PACAP expression in rat sensory and motor neurons is induced by endogenous BDNF. PLoS One. 2014;9:e100730.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Ogata K, Shintani N, Hayata-Takano A, Kamo T, Higashi S, Seiriki K, et al. PACAP enhances axon outgrowth in cultured hippocampal neurons to a comparable extent as BDNF. PLoS One. 2015;10:e0120526.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Conforti L, Gilley J, Coleman MP. Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci. 2014;15:394–409.

    Article  CAS  PubMed  Google Scholar 

  74. Lewis GM, Kucenas S. Perineurial glia are essential for motor axon regrowth following nerve injury. J Neurosci. 2014;34:12762–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Endo A, Nagai N, Urano T, Ihara H, Takada Y, Hashimoto K, et al. Proteolysis of highly polysialylated NCAM by the tissue plasminogen activator-plasmin system in rats. Neurosci Lett. 1998;246:37–40.

    Article  CAS  PubMed  Google Scholar 

  76. Keski-Oja J, Lohi J, Tuuttila A, Tryggvason K, Vartio T. Proteolytic processing of the 72,000-Da type IV collagenase by urokinase plasminogen activator. Exp Cell Res. 1992;202:471–6.

    Article  CAS  PubMed  Google Scholar 

  77. Murphy G, Docherty AJ. The matrix metalloproteinases and their inhibitors. Am J Respir Cell Mol Biol. 1992;7:120–5.

    Article  CAS  PubMed  Google Scholar 

  78. Siconolfi LB, Seeds NW. Mice lacking tPA, uPA, or plasminogen genes showed delayed functional recovery after sciatic nerve crush. J Neurosci. 2001;21:4348–55.

    CAS  PubMed  Google Scholar 

  79. Siconolfi LB, Seeds NW. Mice lacking tissue plasminogen activator and urokinase plasminogen activator genes show attenuated matrix metalloproteases activity after sciatic nerve crush. J Neurosci Res. 2003;74:430–4.

    Article  CAS  PubMed  Google Scholar 

  80. Raoult E, Roussel BD, Bénard M, Lefebvre T, Ravni A, Ali C, et al. Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP. J Neurochem. 2011;119:920–31.

    Article  CAS  PubMed  Google Scholar 

  81. Yamamoto T, Yaksh TL. Effects of colchicine applied to the peripheral nerve on the thermal hyperalgesia evoked with chronic nerve constriction. Pain. 1993;55:227–33.

    Article  CAS  PubMed  Google Scholar 

  82. Yamamoto T, Takahara A. Recent updates of N-type calcium channel blockers with therapeutic potential for neuropathic pain and stroke. Curr Top Med Chem. 2009;9:377–95.

    Article  CAS  PubMed  Google Scholar 

  83. Höke A. Mechanisms of disease: what factors limit the success of peripheral nerve regeneration in humans? Nat Clin Pract Neurol. 2006;2:448–54.

    Article  PubMed  Google Scholar 

  84. Redford EJ, Hall SM, Smith KJ. Vascular changes and demyelination induced by the intraneural injection of tumour necrosis factor. Brain. 1995;118:869–78.

    Article  PubMed  Google Scholar 

  85. Wagner R, Myers RR. Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport. 1996;7:2897–901.

    Article  CAS  PubMed  Google Scholar 

  86. Watkins LR, Maier SF. Glia: a novel drug discovery target for clinical pain. Nat Rev Drug Discov. 2003;2:973–85.

    Article  CAS  PubMed  Google Scholar 

  87. Mor D, Bembrick AL, Austin PJ, Keay KA. Evidence for cellular injury in the midbrain of rats following chronic constriction injury of the sciatic nerve. J Chem Neuroanat. 2011;41:158–69.

    Article  CAS  PubMed  Google Scholar 

  88. Austin PJ, Bembrick AL, Denyer GS, Keay KA. Injury-dependent and disability-specific lumbar spinal gene regulation following sciatic nerve injury in the rat. PLoS One. 2015;10:e0124755.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Austin PJ, Berglund AM, Siu S, Fiore NT, Gerke-Duncan MB, Ollerenshaw SL, et al. Evidence for a distinct neuro-immune signature in rats that develop behavioural disability after nerve injury. J Neuroinflammation. 2015;12:96.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Campana WM, Li X, Shubayev VI, Angert M, Cai K, Myers RR. Erythropoietin reduces Schwann cell TNF-alpha, Wallerian degeneration and pain-related behaviors after peripheral nerve injury. Eur J Neurosci. 2006;23:617–26.

    Article  PubMed  Google Scholar 

  91. Shamash S, Reichert F, Rotshenker S. The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci. 2002;22:3052–60.

    CAS  PubMed  Google Scholar 

  92. Frieboes LR, Palispis WA, Gupta R. Nerve compression activates selective nociceptive pathways and upregulates peripheral sodium channel expression in Schwann cells. J Orthop Res. 2010;28:753–61.

    Article  CAS  PubMed  Google Scholar 

  93. Sándor K, Bölcskei K, McDougall JJ, Schuelert N, Reglodi D, Elekes K, et al. Divergent peripheral effects of pituitary adenylate cyclase-activating polypeptide-38 on nociception in rats and mice. Pain. 2009;141:143–50.

    Article  PubMed  Google Scholar 

  94. Sándor K, Kormos V, Botz B, Imreh A, Bölcskei K, Gaszner B, et al. Impaired nocifensive behaviours and mechanical hyperalgesia, but enhanced thermal allodynia in pituitary adenylate cyclase-activating polypeptide deficient mice. Neuropeptides. 2010;44:363–71.

    Article  PubMed  Google Scholar 

  95. Botz B, Imreh A, Sándor K, Elekes K, Szolcsányi J, Reglődi D, et al. Role of pituitary adenylate-cyclase activating polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions. Peptides. 2013;43:105–12.

    Article  CAS  PubMed  Google Scholar 

  96. Delgado M, Abad C, Martinez C, Juarranz MG, Leceta J, Ganea D, et al. PACAP in immunity and inflammation. Ann N Y Acad Sci. 2003;992:141–57.

    Article  CAS  PubMed  Google Scholar 

  97. Delgado M, Jonakait GM, Ganea D. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit chemokine production in activated microglia. Glia. 2002;39:148–61.

    Article  PubMed  Google Scholar 

  98. Delgado M, Ganea D. Inhibition of endotoxin-induced macrophage chemokine production by VIP and PACAP in vitro and in vivo. Arch Physiol Biochem. 2001;109:377–82.

    Article  CAS  PubMed  Google Scholar 

  99. Delgado M, Munoz-Elias EJ, Gomariz RP, Ganea D. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide enhance IL-10 production by murine macrophages: in vitro and in vivo studies. J Immunol. 1999;162:1707–16.

    CAS  PubMed  Google Scholar 

  100. Stettner M, Lohmann B, Wolffram K, Weinberger JP, Dehmel T, Hartung HP, et al. Interleukin-17 impedes Schwann cell-mediated myelination. J Neuroinflammation. 2014;11:63.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Yu R, Wang J, Li J, Wang Y, Zhang H, Chen J, et al. A novel cyclopeptide from the cyclization of PACAP(1-5) with potent activity towards PAC1 attenuates STZ-induced diabetes. Peptides. 2010;31:1062–7.

    Google Scholar 

  102. Cheng H, Ding Y, Yu R, Chen J, Wu C. Neuroprotection of a novel cyclopeptide C*HSDGIC* from the cyclization of PACAP (1-5) in cellular and rodent models of retinal ganglion cell apoptosis. PLoS One. 2014;9:e108090.

    Google Scholar 

  103. Lamine A, Létourneau M, Doan ND, Maucotel J, Couvineau A, Vaudry H, et al. Characterizations of a synthetic pituitary adenylate cyclase-activating polypeptide analog displaying potent neuroprotective activity and reduced in vivo cardiovascular side effects in a Parkinson’s disease model. Neuropharmacology. 2015.

    Google Scholar 

Download references

Acknowledgments

The economical sources for the realization of this book chapter are from the Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Italy (National Grant–PiTecnoBio PON 01_02464). I would like to thank Dr. Rubina Marzagalli for her help in retrieving literature information and for the preparation of the iconographic material. A further thanks goes to Mr. P. Asero for his technical support.

Authors’ disclosures The author declares that there is no conflict of interests regarding the publication of this chapter.

Author information

Authors and Affiliations

  1. Department of Biomedical and Biotechnological Sciences, Section of Human Anatomy and Histology, University of Catania, Via S. Sofia, 87, Catania, 95123, Italy

    Alessandro Castorina

Authors
  1. Alessandro Castorina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alessandro Castorina .

Editor information

Editors and Affiliations

  1. Department of Anatomy MTA-PTE “Lendulet” PACAP Research Team, University of Pecs, Pecs, Hungary

    Dora Reglodi

  2. Department of Anatomy MTA-PTE “Lendulet” PACAP Research Team, University of Pecs, Pecs, Hungary

    Andrea Tamas

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Castorina, A. (2016). Multiple Actions of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Schwann Cell Biology. In: Reglodi, D., Tamas, A. (eds) Pituitary Adenylate Cyclase Activating Polypeptide — PACAP. Current Topics in Neurotoxicity, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-319-35135-3_28

Download citation

Publish with us

Policies and ethics

Search

Navigation