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PACAP is an Endogenous Protective Factor—Insights from PACAP-Deficient Mice

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widespread neuropeptide with a diverse array of biological functions. Not surprisingly, the lack of endogenous PACAP therefore results in a variety of abnormalities. One of the important effects of PACAP is its neuroprotective and general cytoprotective role. PACAP protects neurons and other tissues against ischemic, toxic, and traumatic lesions. Data obtained from PACAP-deficient mice provide evidence that endogenous PACAP also has protective functions. Mice lacking PACAP are more vulnerable to different in vitro and in vivo insults. The present review summarizes data on the increased sensitivity of PACAP-deficient mice against harmful stimuli. Mice lacking PACAP respond with a higher degree of injury in cerebral ischemia, autoimmune encephalomyelitis, and axonal lesion. Retinal ischemic and excitotoxic injuries also produce increased cell loss in PACAP-deficient mice. In peripheral organs, kidney cell cultures from PACAP-deficient mice are more sensitive to oxidative stress and in vitro hypoxia. In vivo, PACAP-deficient mice have a negative histological outcome and altered cytokine response in kidney and small intestine ischemia/reperfusion injury. Large intestinal inflammation, toxic lesion of the pancreas, and doxorubicin-induced cardiomyopathy are also more severe with a lack of endogenous PACAP. Finally, an increased inflammatory response has been described in subacute endotoxin-induced airway inflammation and in an oxazolone-induced allergic contact dermatitis model. In summary, lack of endogenous PACAP leads to higher vulnerability in a number of injuries in the nervous system and peripheral organs, supporting the hypothesis that PACAP is part of the endogenous cytoprotective machinery.

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References

  • Abad C, Waschek JA (2011) Immunomodulatory roles of VIP and PACAP in models of multiple sclerosis. Curr Pharm Des 17:1025–1035

    Article  PubMed  CAS  Google Scholar 

  • Ago Y, Yoneyama M, Ishihama T et al (2011) Role of endogenous pituitary adenylate cyclase-activating polypeptide in adult hippocampal neurogenesis. Neuroscience 172:554–561

    Article  PubMed  CAS  Google Scholar 

  • Allais A, Burel D, Isaac ER et al (2007) Altered cerebellar development in mice lacking pituitary adenylate cyclase-activating polypeptide. Eur J Neurosci 25:2604–2618

    Article  PubMed  Google Scholar 

  • Alston EN, Parrish DC, Hasan W, Tharp K, Pahlmeyer L, Habecker BA (2011) Cardiac ischemia-reperfusion regulates sympathetic neuropeptide expression through gp130-dependent and independent mechanisms. Neuropeptides 45:33–42

    Article  PubMed  CAS  Google Scholar 

  • Armstrong BD, Abad C, Chhith S et al (2008) Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide. Neuroscience 151:63–73

    Article  PubMed  CAS  Google Scholar 

  • Atlasz T, Szabadfi K, Kiss P et al (2010) Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects. Ann NY Acad Sci 1200:128–139

    Article  PubMed  CAS  Google Scholar 

  • Atlasz T, Babai N, Kiss P et al (2007) Pituitary adenylate cyclase activating polypeptide is protective in bilateral carotid occlusion-induced retinal lesion in rats. Gen Comp Endocrinol 153:108–114

    Article  PubMed  CAS  Google Scholar 

  • Azuma YT, Hagi K, Shintani N et al (2008) PACAP provides colonic protection against dextran sodium sulfate induced colitis. J Cell Physiol 216:111–119

    Article  PubMed  CAS  Google Scholar 

  • Botia B, Jolivel V, Burel D et al (2011) Neuroprotective effects of PACAP against ethanol-induced toxicity in the developing rat cerebellum. Neurotox Res 19:423–434

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Samal B, Hamelink CR et al (2006) Neuroprotection by endogenous and exogenous PACAP following stroke. Regul Pept 137:4–19

    Article  PubMed  CAS  Google Scholar 

  • Dejda A, Jolivel V, Bourgault S et al (2008) Inhibitory effect of PACAP on caspase activity in neuronal apoptosis: a better understanding towards therapeutic applications in neurodegenerative diseases. J Mol Neurosci 36:26–37

    Article  PubMed  CAS  Google Scholar 

  • Dohi K, Mizushima H, Nakajo S et al (2002) Pituitary adenylate cyclase-activating polypeptide (PACAP) prevents hippocampal neurons from apoptosis by inhibiting JNK/SAPK and p38 signal transduction pathways. Regul Pept 109:83–88

    Article  PubMed  CAS  Google Scholar 

  • Elekes K, Sandor K, Moricz A et al (2011) Pituitary adenylate cyclase-activating polypeptide plays an anti-inflammatory role in endotoxin-induced airway inflammation: in vivo study with gene-deleted mice. Peptides 32:1439–1446

    Article  PubMed  CAS  Google Scholar 

  • Endo K, Nakamachi T, Seki T et al (2011) Neuroprotective effect of PACAP against NMDA-induced retinal damage in the mouse. J Mol Neurosci 43:22–29

    Article  PubMed  CAS  Google Scholar 

  • Ferencz A, Racz B, Tamas A et al (2009) Influence of PACAP on oxidative stress and tissue injury following small-bowel autotransplantation. J Mol Neurosci 37:168–176

    Article  PubMed  CAS  Google Scholar 

  • Ferencz A, Kiss P, Gy W et al (2010a) Comparison of intestinal warm ischemic injury in PACAP knockout and wild-type mice. J Mol Neurosci 42:435–442

    Article  PubMed  CAS  Google Scholar 

  • Ferencz A, Gy W, Zs H, Hashimoto H, Baba A, Reglodi D (2010b) Presence of endogenous PACAP-38 ameliorated intestinal cold preservation tissue injury. J Mol Neurosci 42:428–434

    Article  PubMed  CAS  Google Scholar 

  • Gasz B, Racz B, Roth E et al (2006) Pituitary adenylate cyclase activating polypeptide protects cardiomyocytes against oxidative stress-induced apoptosis. Peptides 27:87–94

    Article  PubMed  CAS  Google Scholar 

  • Gaszner B, Kormos V, Kozicz T, Hashimoto H, Reglodi D, Helyes Zs (2012) The behavioral phenotype of pituitary adenylate cyclase-activating polypeptide deficient mice in anxiety and depression tests is accompanied by blunted c-Fos expression in the bed nucleus of the stria terminalis, central projecting Edinger Westphal nucleus, ventral lateral septum, and dorsal raphe nucleus. Neuroscience 202:283–299

    Article  PubMed  CAS  Google Scholar 

  • Gray SL, Cummings KJ, Jirik FR, Sherwood NM (2001) Targeted disruption of the pituitary adenylate cyclase-activating polypeptide gene results in early postnatal death associated with dysfunction of lipid and carbohydrate metabolism. Mol Endocrinol 15:1739–1747

    Article  PubMed  CAS  Google Scholar 

  • Hamelink C, Tjurmina O, Damadzic R et al (2002) Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis. Proc Natl Acad Sci USA 99:461–466

    Article  PubMed  CAS  Google Scholar 

  • Hannibal J (2006) Roles of PACAP-containing retinal ganglion cells in circadian timing. Int Rev Cytol 251:1–39

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto H, Shintani N, Tanaka K et al (2001) Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP). Proc Natl Acad Sci USA 98:13355–13360

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto H, Shintani N, Tanida M, Hayata A, Hashimoto R, Baba A (2011) PACAP is implicated in the stress axes. Curr Pharm Des 17:985–989

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto H, Hashimoto R, Shintani N et al (2009) Depression-like behavior in the forced swimming test in PACAP-deficient mice: amelioration by the atypical antipsychotic risperidone. J Neurochem 110:595–602

    Article  PubMed  CAS  Google Scholar 

  • Hatanaka M, Tanida M, Shintani N et al (2008) Lack of light-induced elevation of renal sympathetic nerve activity and plasma corticosterone levels in PACAP-deficient mice. Neurosci Lett 444:153–156

    Article  PubMed  CAS  Google Scholar 

  • Horvath G, Mark L, Brubel R et al (2010a) Mice deficient in pituitary adenylate cyclase activating polypeptide display increased sensitivity to renal oxidative stress in vitro. Neurosci Lett 469:70–74

    Article  PubMed  CAS  Google Scholar 

  • Horvath G, Racz B, Szakaly P et al (2010b) Mice deficient in neuropeptide PACAP demonstrate increased sensitivity to in vitro kidney hypoxia. Transplant Proc 42:2293–2295

    Article  PubMed  CAS  Google Scholar 

  • Isaac ER, Sherwood NM (2008) Pituitary adenylate cyclase-activating polypeptide (PACAP) is important for embryo implantation in mice. Mol Cell Endocrinol 280:13–19

    Article  PubMed  CAS  Google Scholar 

  • Kato H, Ito A, Kawanokuchi J et al (2004) Pituitary adenylate cyclase activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells. Mult Scler 10:651–659

    Article  PubMed  CAS  Google Scholar 

  • Kawaguchi C, Tanaka K, Isojima Y et al (2003) Changes in light-induced phase shift of circadian rhythm in mice lacking PACAP. Biochem Biophys Res Commun 310:169–175

    Article  PubMed  CAS  Google Scholar 

  • Kemeny A, Reglodi D, Cseharovszky R et al (2010) Pituitary adenylate cyclase-activating polypeptide deficiency enhances oxazolone-induced allergic contact dermatitis in mice. J Mol Neurosci 42:443–449

    Article  PubMed  CAS  Google Scholar 

  • Larsen JO, Hannibal J, Knudsen SM, Fahrenkrug J (1997) Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) in the mesencephalic trigeminal nucleus of the rat after transection of the masseteric nerve. Mol Brain Res 46:109–117

    Article  PubMed  CAS  Google Scholar 

  • Li M, Maderdrut JL, Lertora JJ, Arimura A, Batuman V (2008) Renoprotection by pituitary adenylate cyclase-activating polypeptide in multiple myeloma and other kidney diseases. Regul Pept 145:24–32

    Article  PubMed  CAS  Google Scholar 

  • Li M, Balamuthusamy S, Khan AM, Maderdrut JL, Simon EE, Batuman V (2011) Pituitary adenylate cyclase-activating polypeptide prevents cisplatin-induced renal failure. J Mol Neurosci 43:58–66

    Article  PubMed  CAS  Google Scholar 

  • Mabuchi T, Shintani N, Matsumura S et al (2004) Pituitary adenylate cyclase-activating polypeptide is required for the development of spinal sensitization and induction of neuropathic pain. J Neurosci 24:7283–7291

    Article  PubMed  CAS  Google Scholar 

  • Markovics A, Kormos V, Gaszner B et al (2012) Pituitary adenylate cyclase-activating polypeptide plays a key role in nitroglycerol-induced trigeminovascular activation in mice. Neurobiol Dis 45:633–644

    Article  PubMed  CAS  Google Scholar 

  • Marquez P, Bebawy D, Lelievre V et al (2009) The role of endogenous PACAP in motor stimulation and conditioned place preference induced by morphine in mice. Psychopharmacology 204:457–463

    Article  PubMed  CAS  Google Scholar 

  • Mester L, Szabo A, Atlasz T et al (2009) Protection against chronic hypoperfusion-induced retinal neurodegeneration by PARP inhibition via activation of PI3-kinase Akt pathway and suppression of JNK and p38 MAP kinases. Neurotox Res 16:68–76

    Article  PubMed  CAS  Google Scholar 

  • Miyata A, Arimura A, Dahl RR et al (1989) Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 164:567–574

    Article  PubMed  CAS  Google Scholar 

  • Moller K, Reimer M, Ekblad E et al (1997) The effects of axotomy and preganglionic denervation on the expression of pituitary adenylate cyclase activating polypeptide (PACAP), galanin and PACAP type 1 receptors in the rat superior cervical ganglion. Brain Res 775:166–182

    Article  PubMed  CAS  Google Scholar 

  • Mori H, Nakamachi T, Ohtaki H et al (2010) Cardioprotective effect of endogenous pituitary adenylate cyclase-activating polypeptide on doxorubicin-induced cardiomyopathy in mice. Circ J 74:1183–1190

    Article  PubMed  CAS  Google Scholar 

  • Nakamachi T, Farkas J, Watanabe J et al (2011) Role of PACAP in neural stem/progenitor cell and astrocyte—from neural development to neural repair. Curr Pharm Des 17:973–984

    Article  PubMed  CAS  Google Scholar 

  • Nakamachi T, Ohtaki H, Yofu S et al (2010) Endogenous pituitary adenylate cyclase activating polypeptide is involved in suppression of edema in the ischemic brain. Acta Neurochir Suppl 106:43–46

    Article  PubMed  Google Scholar 

  • Nakata M, Shintani N, Hashimoto H, Baba A (2010) Intra-islet PACAP protects pancreatic beta-cells against glucotoxicity and lipotoicity. J Mol Neurosci 42:404–410

    Article  PubMed  CAS  Google Scholar 

  • Nemetz N, Abad C, Lawson G et al (2008) Induction of colitis and rapid development of colorectal tumors in mice deficient in the neuropeptide PACAP. Int J Cancer 122:1803–1809

    Article  PubMed  CAS  Google Scholar 

  • Ogawa T, Nakamachi T, Ohtaki H et al (2005) Monoaminergic neuronal development is not affected in PACAP-gene-deficient mice. Regul Pept 126:103–108

    Article  PubMed  CAS  Google Scholar 

  • Ohtaki H, Nakamachi T, Dohi K et al (2006) Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6. Proc Natl Acad Sci USA 103:7488–7493

    Article  PubMed  CAS  Google Scholar 

  • Ohtaki H, Nakamachi T, Dohi K, Shioda S (2008) Role of PACAP in ischemic neural death. J Mol Neurosci 36:16–25

    Article  PubMed  CAS  Google Scholar 

  • Ohtaki H, Satoh A, Nakamachi T et al (2010) Regulation of oxidative stress by pituitary adenylate cyclase-activating polypeptide (PACAP) mediated by PACAP receptor. J Mol Neurosci 42:397–403

    Article  PubMed  CAS  Google Scholar 

  • Onoue S, Hanato J, Yamada S (2008) Pituitary adenylate cyclase-activating polypeptide attenuates streptozotocin-induced apoptotic death of RIN-m5F cells through regulation of Bcl-2 family protein mRNA expression. FEBS J 275:5542–5551

    Article  PubMed  CAS  Google Scholar 

  • Pinhasov A, Nesher E, Gross M, Turgeman G, Kreinin A, Yadid G (2011) The role of the PACAP signaling system in depression. Curr Pharm Des 17:990–1001

    Article  PubMed  CAS  Google Scholar 

  • Racz B, Gasz B, Gallyas F et al (2008) PKA-Bad-14-3-3 and Akt-Bad-14-3-3 signaling pathways are involved in the protective effects of PACAP against ischemia/reperfusion-induced cardiomyocyte apoptosis. Regul Pept 145:105–115

    Article  PubMed  CAS  Google Scholar 

  • Racz B, Reglodi D, Horvath G et al (2010) Protective effect of PACAP against doxorubicin-induced cell death in cardiomyocyte culture. J Mol Neurosci 42:419–427

    Article  PubMed  CAS  Google Scholar 

  • Reglodi D, Tamas A, Somogyvari-Vigh A et al (2002) Effects of pretreatment with PACAP on the infarct size and functional outcome in rat permanent focal cerebral ischemia. Peptides 23:2227–2234

    Article  PubMed  CAS  Google Scholar 

  • Reglodi D, Kiss P, Lubics A, Tamas A (2011) Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo. Curr Pharm Des 17:962–972

    Article  PubMed  CAS  Google Scholar 

  • Reglodi D, Kiss P, Horvath G et al (2012) Effects of pituitary adenylate cyclase activating polypeptide in the urinary system, with special emphasis on its protective effects in the kidney. Neuropeptides 46:61–70

    Article  PubMed  CAS  Google Scholar 

  • Riek-Burchardt M, Kolodziej A, Henrich-Noack P, Reymann KG, Hollt V, Stumm R (2010) Differential regulation of CXCL12 and PACAP mRNA expression after focal and global ischemia. Neuropharmacology 58:199–207

    Article  PubMed  CAS  Google Scholar 

  • Sakurai Y, Shintani N, Hayata A, Hashimoto H, Baba A (2011a) Trophic effects of PACAP on pancreatic islets: a mini-review. J Mol Neurosci 43:3–7

    Article  PubMed  CAS  Google Scholar 

  • Sakurai Y, Shintani N, Arimori A et al (2011b) Cerulein-induced acute pancreatitis in PACAP knockout mice. J Mol Neurosci 43:8–15

    Article  PubMed  CAS  Google Scholar 

  • Sandor K, Kormos V, Botz B et al (2010) Impaired nocifensive behaviours and mechanical hyperalgesia, but enhanced thermal allodynia in pituitary adenylate cyclase-activating polypeptide deficient mice. Neuropeptides 44:363–371

    Article  PubMed  CAS  Google Scholar 

  • Sano H, Miyata A, Horio T, Nishikimi T, Matsuo H, Kangawa K (2002) The effect of pituitary adenylate cyclase activating polypeptide on cultured rat cardiocytes as a cardioprotective factor. Regul Pept 109:107–113

    Article  PubMed  CAS  Google Scholar 

  • Seaborn T, Masmoudi-Kouli O, Fournier A, Vaudry H, Vaudry D (2011) Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis. Curr Pharm Des 17:204–214

    Article  PubMed  CAS  Google Scholar 

  • Shin CM, Chung YH, Kim MJ, Cha CI (2001) Spatial and temporal distribution of pituitary adenylate cyclase activating polypeptide in gerbil global cerebral ischemia. Neurosci Lett 309:53–56

    Article  PubMed  CAS  Google Scholar 

  • Shintani N, Mori W, Hashimoto H et al (2002) Defects in reproductive functions in PACAP-deficient female mice. Regul Pept 109:45–48

    Article  PubMed  CAS  Google Scholar 

  • Skoglosa Y, Lewen A, Takei N, Hillered L, Lindholm D (1999) Regulation of pituitary adenylate cyclase activating polypeptide and its receptor type I after traumatic brain injury: comparison with brain-derived neurotrophic factor and the induction of neuronal cell death. Neuroscience 90:235–247

    Article  PubMed  CAS  Google Scholar 

  • Somogyvari-Vigh A, Reglodi D (2004) Pituitary adenylate cyclase activating polypeptide: a potential neuroprotective peptide. Curr Pharm Des 10:2861–2689

    Article  PubMed  CAS  Google Scholar 

  • Stroth N, Holighaus Y, Ait-Ali D, Eiden LE (2011) PACAP: a master regulator of neuroendocrine stress circuits and the cellular stress response. Ann NY Acad Sci 1220:49–59

    Article  PubMed  CAS  Google Scholar 

  • Stumm R, Kolodziej A, Prinz V, Endres M, Wu DF, Hollt V (2007) Pituitary adenylate cyclase activating polypeptide is up-regulated in cortical pyramidal cells after focal cerebral ischemia and protects neurons from mild hypoxic/ischemic damage. J Neurochem 103:1666–1681

    Article  PubMed  CAS  Google Scholar 

  • Szabadfi K, Atlasz T, Kiss P et al (2012) Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) are more susceptible to retinal ischemic injury in vivo. Neurotox Res 21:41–48

    Article  PubMed  CAS  Google Scholar 

  • Szakaly P, Kiss P, Lubics A et al (2008) Effects of PACAP on survival and renal morphology in rats subjected to renal ischemia/reperfusion. J Mol Neurosci 36:89–96

    Article  PubMed  CAS  Google Scholar 

  • Szakaly P, Laszlo E, Kovacs K et al (2011) Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) show increased susceptibility to in vivo renal ischemia/reperfusion injury. Neuropeptides 45:113–121

    Article  PubMed  CAS  Google Scholar 

  • Tamas A, Reglodi D, Szanto Z, Borsiczky B, Nemeth J, Lengvari I (2002) Comparative neuroprotective effects of preischemic PACAP and VIP administration in permanent occlusion of the middle cerebral artery in rats. Neuroendocrinol Lett 23:249–254

    PubMed  CAS  Google Scholar 

  • Tamas A, Szabadfi K, Nemeth A et al (2012) Comparative examination of inner ear in wild type and pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice. Neurotox Res 21:435–444

    Article  PubMed  CAS  Google Scholar 

  • Tan YV, Abad C, Lopez R et al (2009) Pituitary adenylyl cyclase activating polypeptide is an intrinsic regulator of Treg abundance and protects against experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 106:2012–2017

    Article  PubMed  CAS  Google Scholar 

  • Tanaka K, Hashimoto H, Shintani N, Yamamoto A, Baba A (2004) Reduced hypothermic and hypnotic responses to ethanol in PACAP-deficient mice. Regul Pept 123:95–98

    Article  PubMed  CAS  Google Scholar 

  • Tomimoto S, Ojika T, Shintani N et al (2008) Markedly reduced white adipose tissue and increased insulin sensitivity in Adcyap1-deficient mice. J Pharmacol Sci 107:41–48

    Article  PubMed  CAS  Google Scholar 

  • Tsuchikawa D, Nakamachi T, Tsuchida M, Wada Y et al (2011) The neuroprotective effect of endogenous PACAP on spinal cord injury. Abstract. Presented at the 10th international Symposiumson VIP, PACAP and related peptides, 2011 Eilat, Israel

  • Vaudry D, Hamelink C, Damadzic R, Eskay RL, Gonzalez B, Eiden LE (2005) Endogenous PACAP acts as a stress response peptide to protect cerebellar neurons from ethanol or oxidative insult. Peptides 26:2518–2524

    Article  PubMed  CAS  Google Scholar 

  • Vaudry D, Falluel-Morel A, Bourgault A et al (2009) Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharm Rev 61:283–357

    Article  PubMed  CAS  Google Scholar 

  • Vincze A, Reglodi D, Zs H, Hashimoto H, Shintani H, Abraham H (2011) Role of pituitary adenylate cyclase activating polypeptide (PACAP) in myelination of the rodent brain: lessons from PACAP-deficient mice. Int J Dev Neurosci 29:923–935

    Article  PubMed  CAS  Google Scholar 

  • Wilson RJ, Cummings KJ (2008) Pituitary adenylate cyclase-activating polypeptide is vital foe neonatal survival and the neuronal control of breathing. Respir Physiol Neurobiol 164:168–178

    Article  PubMed  CAS  Google Scholar 

  • Yamada K, Matsuzaki S, Hattori T et al (2010) Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations. PLoS One 5:e8596

    Article  PubMed  Google Scholar 

  • Zhang YZ, Hannibal J, Zhao Q et al (1996) Pituitary adenylate cyclase activating peptide expression in the rat dorsal root ganglia: up-regulation after peripheral nerve injury. Neuroscience 74:1099–1110

    PubMed  CAS  Google Scholar 

  • Zhang Y, Danielsen N, Sundler F, Mulder H (1998) Pituitary adenylate cyclase-activating peptide is upregulated in sensory neurons by inflammation. Neuroreport 9:2833–2836

    Article  PubMed  CAS  Google Scholar 

  • Zhou X, Rodriguez WI, Casillas RA et al (1999) Axotomy-induced changes in pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP receptor gene expression in the adult rat facial motor nucleus. J Neurosci Res 57:953–961

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by OTKA K72592, CNK78480; F67830, T73044, Bolyai Scholarship, Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science, Richter Gedeon Centenary Foundation, SROP-4.2.1.B-10/2/KONV-2010-0002, SROP-4.2.2/B-10/1-2010-0029, Funding Program for Next Generation World-Leading Researchers (established by the Council for Science and Technology Policy, Cabinet Office, Government of Japan), and by the Ross University Research Fund and Momentum Program of the Hungarian Academy of Sciences.

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Authors and Affiliations

  1. Department of Anatomy, PTE-MTA “Lendulet” PACAP Research Group, University of Pecs, 7624, Pecs, Szigeti u 12, Hungary

    D. Reglodi, P. Kiss, G. Horvath, A. Lubics, E. Laszlo, J. Farkas, A. Matkovits, R. Brubel, A. Vincze & A. Tamas

  2. Department of Experimental Zoology and Neurobiology, University of Pecs, Pecs, Hungary

    K. Szabadfi & R. Gabriel

  3. Department of Sportbiology, University of Pecs, Pecs, Hungary

    T. Atlasz

  4. Surgery Clinic, University of Pecs, Pecs, Hungary

    P. Szakaly

  5. Department of Dentistry, Oral and Maxillofacial Surgery, University of Pecs, Pecs, Hungary

    B. Sandor

  6. Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

    H. Hashimoto

  7. Center for Child Mental Development, United Graduate School of Child Development, Kanazawa University and Hamamatsu University School of Medicine, Osaka University, Osaka, Japan

    H. Hashimoto

  8. Department of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University, Osaka, Japan

    H. Hashimoto

  9. Department of Surgical Research and Techniques, Semmelweis University, Budapest, Hungary

    A. Ferencz

  10. Department of Pharmacology and Pharmacotherapy, University of Pecs, Pecs, Hungary

    Z. Helyes

  11. Department of Anatomy, Ross University School of Medicine, Roseau, Dominica, West Indies

    L. Welke

  12. Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA

    A. Lakatos

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  1. D. Reglodi
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  2. P. Kiss
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  20. A. Tamas
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Correspondence to D. Reglodi.

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Reglodi, D., Kiss, P., Szabadfi, K. et al. PACAP is an Endogenous Protective Factor—Insights from PACAP-Deficient Mice. J Mol Neurosci 48, 482–492 (2012). https://doi.org/10.1007/s12031-012-9762-0

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  • DOI: https://doi.org/10.1007/s12031-012-9762-0

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