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Mice Deficient in Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) are More Susceptible to Retinal Ischemic Injury In Vivo

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Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroprotective peptide exerting protective effects in neuronal injuries. We have provided evidence that PACAP is neuroprotective in several models of retinal degeneration in vivo. Our previous studies showed that PACAP treatment ameliorated the damaging effects of chronic hypoperfusion modeled by permanent bilateral carotid artery occlusion. We have also demonstrated in earlier studies that treatment with PACAP antagonists further aggravates retinal lesions. It has been shown that PACAP deficient mice have larger infarct size in cerebral ischemia. The aim of this study was to compare the degree of retinal damage in wild type and PACAP deficient mice in ischemic retinal insult. Mice underwent 10 min of bilateral carotid artery occlusion followed by 2-week reperfusion period. Retinas were then processed for histological analysis. It was found that PACAP deficient mice had significantly greater retinal damage, as shown by the thickness of the whole retina, the morphometric analysis of the individual retinal layers, and the cell numbers in the inner nuclear and ganglion cell layers. Exogenous PACAP administration could partially protect against retinal degeneration in PACAP deficient mice. These results clearly show that endogenous PACAP reacts as a stress-response peptide that is necessary for endogenous protection against different retinal insults.

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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 

  • Allais A, Burel D, Isaac ER, Gray SL, Basille M, Ravni A, Sherwood NM, Vaudry H, Gonzalez BJ (2007) Altered cerebellar development in mice lacking pituitary adenylate cyclase-activating polypeptide. Eur J Neurosci 25:2604–2618

    Article  PubMed  Google Scholar 

  • Armstrong BD, Abad C, Chhith S, Cheung-Lau G, Hajji OE, Nobuta H, Waschek JA (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, Babai N, Reglodi D, Kiss P, Tamas A, Bari F, Domoki F, Gabriel R (2007a) Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration. Neurotox Res 12:105–111

    Article  PubMed  CAS  Google Scholar 

  • Atlasz T, Babai N, Kiss P, Reglodi D, Tamas A, Szabadfi K, Toth G, Hegyi O, Lubics A, Gabriel R (2007b) 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 

  • Atlasz T, Szabadfi K, Reglodi D, Kiss P, Tamas A, Toth G, Molnar A, Szabo K, Gabriel R (2009) Effects of pituitary adenylate cyclase activating polypeptide (PACAP1–38) and its fragments on retinal degeneration induced by neonatal MSG treatment. Ann NY Acad Sci 1163:348–352

    Article  PubMed  CAS  Google Scholar 

  • Atlasz T, Szabadfi K, Kiss P, Tamas A, Toth G, Reglodi D, Gabriel R (2010a) Evaluation of the protective effects of PACAP with cell-specific markers in ischemia-induced retinal degeneration. Brain Res Bull 81:497–504

    Article  PubMed  CAS  Google Scholar 

  • Atlasz T, Szabadfi K, Kiss P, Racz B, Gallyas F, Tamas A, Gaal V, Marton Zs, Gabriel R, Reglodi D (2010b) 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, Szabadfi K, Kiss P, Marton Zs, Griecs M, Hamza L, Gaal V, Biro Zs, Tamas A, Hild G, Nyitrai M, Toth G, Reglodi D, Gabriel R (2011) Effects of PACAP in UV-A radiation-induced retinal degeneration models in rats. J Mol Neurosci 43:51–57

    Article  PubMed  CAS  Google Scholar 

  • Barnett NL, Osborne NN (1995) Prolonged bilateral carotid artery occlusion induces electrophysiological and immunohistochemical changes to the rat retina without causing histological damage. Exp Eye Res 61:83–90

    Article  PubMed  CAS  Google Scholar 

  • Bek T (2009) Inner retinal ischaemia: current understanding and needs for further investigations. Acta Ophthalmol 87:362–367

    Article  PubMed  Google Scholar 

  • Botia B, Jolivel V, Burel D, Le Joncour V, Roy V, Naassila M, Benard M, Fournier A, Vaudry H, Vaudry D (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, Xiang CC, Chen Y, Chen M, Vaudry D, Brownstein MJ, Hallenbeck JM, Eiden LE (2006) Neuroprotection by endogenous and exogenous PACAP following stroke. Regul Pept 137:4–19

    Article  PubMed  CAS  Google Scholar 

  • Cummings KJ, Pendlebury JD, Sherwood NM, Wilson RJ (2004) Sudden neonatal death in PACAP-deficient mice is associated with reduced respiratory chemoresponse and susceptibility to apnoea. J Physiol 555:15–26

    Article  PubMed  CAS  Google Scholar 

  • Davidson CM, Pappas BA, Stevens WD, Fortin T, Bennett SA (2000) Chronic cerebral hypoperfusion: loss of papillary reflex, visual impairment and retinal neurodegeneration. Brain Res 859:96–103

    Article  PubMed  CAS  Google Scholar 

  • Dejda A, Seaborn T, Bourgault S, Touzani O, Fournier A, Vaudry H, Vaudry D (2011) PACAP and a novel stable analog protect rat brain from ischemia: insights into the mechanisms of action. Peptides 32:1207–1216

    Article  PubMed  CAS  Google Scholar 

  • Dimitriu C, Bach M, Lagrèze WA, Jehle T (2008) Methylprednisolone fails to preserve retinal ganglion cells and visual function after ocular ischemia in rats. Invest Ophthalmol Vis Sci 49:5003–5007

    Article  PubMed  Google Scholar 

  • Endo K, Nakamachi T, Seki T, Kagami N, Wada Y, Nakamura K, Kishimoto K, Hori M, Tsuchikawa D, Shintani N, Hashimoto H, Baba A, Koide R, Shioda S (2011) Neuroprotective effect of PACAP against NMDA-induced retinal damage in the mouse. J Mol Neurosci 43:22–29

    Article  PubMed  CAS  Google Scholar 

  • Farkas E, Luiten PG, Bari F (2007) Permanent bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 54:162–180

    Article  PubMed  CAS  Google Scholar 

  • Feigl B (2009) Age-related maculopathy-linking aetiology and pathophysiological changes to the ischaemia hypothesis. Prog Retin Eye Res 28:63–86

    Article  PubMed  CAS  Google Scholar 

  • Ferencz A, Kiss P, Weber G, Helyes Zs, Shintani N, Baba A, Reglodi D (2010) Comparison of intestinal warm ischemic injury in PACAP knock-out and wild-type mice. J Mol Neurosci 42:435–442

    Article  PubMed  CAS  Google Scholar 

  • Gray SL, Yamaguchi N, Vencova P, Sherwood NM (2002) Temperature-sensitive phenotype in mice lacking pituitary adenylate cyclase activating polypeptide. Endocrinology 143:3946–3954

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto H, Shintani N, Tanaka K, Mori W, Hirose M, Matsuda T, Sakaue M, Miyazaki J, Niwa H, Tashiro F, Yamamoto K, Koga K, Tomimoto S, Kunugi A, Suetake S, Baba A (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, Hashimoto R, Shintani N, Tanaka K, Yamamoto A, Hatanaka M, Guo X, Morita M, Nagai K, Takeda M, Baba A (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, Isojima Y, Kawaguchi C, Hashimoto H, Kakuda M, Haba R, Nagai K, Baba A (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 

  • 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 

  • Kawaguchi C, Isojima Y, Shintani N, Hatanaka M, Guo X, Okumura N, Nagai K, Hashimoto H, Baba A (2010) PACAP-deficient mice exhibit light parameter-dependent abnormalities on nonvisual photoreception and early activity onset. PLoS One 5:e9286

    Article  PubMed  Google Scholar 

  • Kemeny A, Reglodi D, Cseharovszky R, Hashimoto H, Baba A, Szolcsanyi J, Helyes Zs (2010) Pituitary adenylate cyclase activating deficiency enhances oxazolone-induced allergic contact dermatitis in mice. J Mol Neurosci 42:443–449

    Article  PubMed  CAS  Google Scholar 

  • Laburthe M, Couvineau A, Tan V (2007) Class II G protein/coupled receptors for VIP and PACAP: structure, models of activation and pharmacology. Peptides 28:1631–1639

    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 

  • Lelong DC, Bieche I, Perez E, Bigot K, Leemput J, Laurendeau I, Vidaud M, Jais JP, Menasche M, Abitbol M (2007) Novel mouse model of mononuclear amaurosis fugax. Stroke 38:3237–3244

    Article  PubMed  Google Scholar 

  • Liu Z, Qiu YH, Li B, Ma SH, Peng YP (2011) Neuroprotection of interleukin-6 against NMDA-induced apoptosis and its signal-transduction mechanism. Neurotox Res 19:484–495

    Article  PubMed  CAS  Google Scholar 

  • Matsuyama S, Matsumoto A, Hashimoto H, Shintani N, Baba A (2003) Impaired long-term potentiation in vivo in the dentate gyrus of pituitary adenylate cyclase activating polypeptide (PACAP) or PACAP type 1 receptor-mutant mice. Neuroreport 14:2095–2098

    Article  PubMed  CAS  Google Scholar 

  • Mester L, Szabo A, Atlasz T, Szabadfi K, Reglodi D, Kiss P, Racz B, Tamas A, Gallyas F, Sumegi B, Hocsak E, Gabriel R, Kovacs K (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, Minamino N, Uehara A, Jiang L, Culler MD, Coy DH (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 

  • Moren H, Undren P, Gesslein B, Olivecrona G, Andreasson S, Malmsjo M (2009) The porcine retinal vasculature can be accessed using an endovascular approach, a new experimental model for retina ischemia. Invest Ophthalmol Vis Sci 50:5504–5510

    Article  PubMed  Google Scholar 

  • Nakamachi T, Ohtaki H, Yofu S, Watanabe J, Mori H, Sato A, Hashimoto H, Shintani N, Baba A, Shioda S (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 

  • Nakamachi T, Farkas J, Watanabe J, Ohtaki H, Dohi K, Arata S, Shioda S (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 

  • Nakata M, Kohno D, Shintani N, Nemoto Y, Hashimoto H, Baba A, Yada T (2004) PACAP deficient mice display reduced carbohydrate intake and PACAP activates NPY-containing neurons in the rat hypothalamic arcuate nucleus. Neurosci Lett 370:252–256

    Article  PubMed  CAS  Google Scholar 

  • Nakatani M, Seki T, Shinohara Y, Taki C, Nichimura S, Takaki A, Shioda S (2006) Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates production of interleukin-6 in rat Muller cells. Peptides 27:1871–1876

    Article  PubMed  CAS  Google Scholar 

  • Ohtaki H, Nakamachi T, Dohi K, Aizawa Y, Takaki A, Hodoyama K, Yofu S, Hashimoto H, Shintani N, Baba A, Kopf M, Iwakura Y, Matsuda K, Arimura A, Shioda S (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, Yofu S, Dohi K, Mori H, Ohara K, Miyamoto K, Hashimoto H, Shintani N, Baba A, Matsunaga M, Shioda S (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 

  • Oliff HS, Coyle P, Weber E (1997) Rat strain and vendor differences in collateral anastomoses. J Cereb Blood Flow Metab 17:571–576

    Article  PubMed  CAS  Google Scholar 

  • Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M, Melena J (2004) Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res 23:91–147

    Article  PubMed  CAS  Google Scholar 

  • Racz B, Gallyas F Jr, Kiss P, Toth G, Hegyi O, Gasz B, Borsiczky B, Ferencz A, Roth E, Tamas A, Lengvari I, Lubics A, Reglodi D (2006) The neuroprotective effects of PACAP in monosodium glutamate-induced retinal lesion involves inhibition of proapoptotic signaling pathways. Regul Pept 137:20–26

    Article  PubMed  CAS  Google Scholar 

  • Racz B, Gallyas F Jr, Kiss P, Tamas A, Lubics A, Lengvari I, Roth E, Toth G, Hegyi O, Verzar Z, Fabricsek C, Reglodi D (2007) Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the PKA-Bad-14–3-3 signaling pathway in glutamate-induced retinal injury in neonatal rats. Neurotox Res 12:95–104

    Article  PubMed  CAS  Google Scholar 

  • Reglodi D, Tamas A, Somogyvari-Vigh A, Szanto Z, Kertes E, Lenard L, Arimura A, Lengvari I (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, Fabian Zs, Tamas A, Lubics A, Szeberenyi J, Alexy T, Toth K, Marton Zs, Borsiczky B, Roth E, Szalontay L, Lengvari I (2004) Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals. Regul Pept 123:51–59

    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 

  • Sandor K, Kormos V, Botz B, Imreh A, Bolcskei K, Gaszner B, Markovics A, Szolcsanyi J, Shintani N, Hashimoto H, Baba A, Reglodi D, Helyes Zs (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 

  • 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 

  • Seki T, Shioda S, Ogino D, Nakai Y, Arimura A, Koide R (1997) Distribution and ultrastructural localization of a receptor for pituitary adenylate cyclase activating polypeptide and its mRNA in the rat retina. Neurosci Lett 238:127–130

    Article  PubMed  CAS  Google Scholar 

  • Seki T, Shioda S, Izumi S, Arimura A, Koide R (2000a) Electron microscopic observation of pituitary adenylate cyclase activating polypeptide (PACAP)-containing neurons in the rat retina. Peptides 21:109–113

    Article  PubMed  CAS  Google Scholar 

  • Seki T, Izumi S, Shioda S, Zhou CJ, Arimura A, Koide R (2000b) Gene expression for PACAP receptor mRNA in the rat retina by in situ hybridization and in situ RT-PCR. Ann NY Acad Sci 921:366–369

    Article  PubMed  CAS  Google Scholar 

  • Seki T, Nakatani M, Taki C, Shinohara Y, Ozawa M, Nishimura S, Ito H, Shioda S (2006) Neuroprotective effect of PACAP against kainic acid-induced neurotoxicity in rat retina. Ann NY Acad Sci 1070:531–534

    Article  PubMed  CAS  Google Scholar 

  • Seki T, Itoh H, Nakamachi T, Shioda S (2008) Suppression of ganglion cell death by PACAP following optic nerve transection in the rat. J Mol Neurosci 36:57–60

    Article  PubMed  CAS  Google Scholar 

  • Seki T, Itoh H, Nakamachi T, Endo K, Wada Y, Nakamura K, Shioda S (2011) Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure. J Mol Neurosci 43:30–34

    Article  PubMed  CAS  Google Scholar 

  • Shazly TA, Latina MA (2009) Neovascular glaucoma: etiology, diagnosis and prognosis. Semin Ophthalmol 24:113–121

    Article  PubMed  Google Scholar 

  • Shioda S, Ozawa H, Dohi K, Mizushima H, Matsumoto K, Nakajo S, Takaki A, Zhou CJ, Nakai Y, Arimura A (1998) PACAP protects hippocampal neurons against apoptosis: involvement of JNK/SAPK signaling pathway. Ann NY Acad Sci 865:111–117

    Article  PubMed  CAS  Google Scholar 

  • Shioda S, Ohtaki H, Nakamachi T, Dohi K, Watanabe J, Nakajo S, Arata S, Kitamura S, Okuda H, Takenoya F, Kitamura Y (2006) Pleiotropic functions of PACAP in the CNS: neuroprotection and neurodevelopment. Ann NY Acad Sci 1070:550–560

    Article  PubMed  CAS  Google Scholar 

  • Silveira MS, Costa MR, Bozza M, Linden R (2002) Pituitary adenylate cyclase activating polypeptide prevents induced cell death in retinal tissue through activation of cyclic AMP-dependent protein kinase. J Biol Chem 277:16075–16080

    Article  PubMed  CAS  Google Scholar 

  • Somogyvari-Vigh A, Reglodi D (2004) Pituitary adenylate cyclase activating polypeptide: a potential neuroprotective peptide. Curr Pharm Des 10:2861–2889

    Article  PubMed  CAS  Google Scholar 

  • Szabadfi K, Atlasz T, Reglodi D, Kiss P, Danyadi B, Fekete EM, Zorilla EP, Tamas A, Szabo K, Gabriel R (2009) Urocortin 2 protects against retinal degeneration following bilateral common carotid artery occlusion in the rat. Neurosci Lett 455:42–45

    Article  PubMed  CAS  Google Scholar 

  • Szabadfi K, Mester L, Reglodi D, Kiss P, Babai N, Racz B, Kovacs K, Szabo A, Tamas A, Gabriel R, Atlasz T (2010) Novel neuroprotective strategies in ischemic retinal lesions. Int J Mol Sci 11:544–561

    Article  PubMed  CAS  Google Scholar 

  • Szakaly P, Laszlo E, Kovacs K, Racz B, Horvath G, Ferencz A, Lubics A, Kiss P, Tamas A, Brubel R, Opper B, Baba A, Hashimoto H, Farkas J, Matkovits A, Magyarlaki T, Helyes Zs, Reglodi D (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, Gabriel R, Racz B, Denes V, Kiss P, Lubics A, Lengvari I, Reglodi D (2004) Effects of pituitary adenylate cyclase activating polypeptide in retinal degeneration induced by monosodium-glutamate. Neurosci Lett 372:110–113

    Article  PubMed  CAS  Google Scholar 

  • Tan YV, Abad C, Lopez R, Dong H, Liu S, Lee A, Gomariz RP, Leceta J, Waschek JA (2009) Targeted gene deletion reveals that pituitary adenylyl cyclase activating polypeptide is an intrinsic regulator of Treg abundance in mice and plays a protective role in experimental autoimmune encephalomyelitis. Proc Natl Acac Sci USA 106:2012–2017

    Article  CAS  Google Scholar 

  • Tomimoto S, Ojika T, Shintani N, Hashimoto H, Hamagami K, Ikeda K, Nakata M, Yada T, Sakurai Y, Shimada T, Morita Y, Ishida C, Baba A (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 

  • Uchida D, Arimura A, Somogyvari-Vigh A, Shioda S, Banks WA (1996) Prevention of ischemia-induced death of hippocampal neurons by pituitary adenylate cyclase activating polypeptide. Brain Res 736:280–286

    Article  PubMed  CAS  Google Scholar 

  • Varga B, Szabadfi K, Kiss P, Fabian E, Tamas A, Griecs M, Gabriel R, Reglodi D, Kemeny-Beke A, Pamer Z, Biro Z, Tosaki A, Atlasz T, Juhasz B (2011) PACAP improves functional outcome in excitotoxic retinal lesion: an electroretinographic study. J Mol Neurosci 43:44–50

    Article  PubMed  CAS  Google Scholar 

  • 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, Basille M, Burel D, Wurtz O, Fournier A, Chow BK, Hashimoto H, Galas L, Vaudry H (2009) Pituitary adenylate cyclase activating polypeptide and its receptors: 20 years after the discovery. Pharm Rev 61:283–357

    Article  PubMed  CAS  Google Scholar 

  • Vidal-Sanz M, Lafuente M, Sobrado-Calvo P, Selles-Navarro I, Rodriguez E, Mayor-Torroglosa S, Villegas-Perez MP (2000) Death and neuroprotection of retinal ganglion cells after different types of injury. Neurotox Res 2:215–227

    Article  PubMed  CAS  Google Scholar 

  • Waschek JA (2002) Multiple actions of pituitary adenylyl cyclase activating peptide in nervous system development and regeneration. Dev Neurosci 24:14–23

    Article  PubMed  CAS  Google Scholar 

  • Yamada K, Matsuzaki S, Hattori T, Kuwahara R, Taniguchi M, Hashimoto H, Shintani N, Baba A, Kumamoto N, Yamada K, Yoshikawa T, Katayama T, Tohyama M (2010) Increased stathmin1 expression in the dentate gyrus of mice causes abnormal axonal arborizations. PLoS One 5:e8596

    Article  PubMed  Google Scholar 

  • Yamamoto H, Schmidt-Kastner R, Hamasaki DI, Yamamoto H, Parel JM (2006) Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats. Exp Eye Res 82:767–779

    Article  PubMed  CAS  Google Scholar 

  • Zhang YZ, Hannibal J, Zhao Q, Moller K, Danielsen N, Fahrenkrug J, Sundler F (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 

  • Zheng L, Gong B, Hatala DA, Kern TS (2007) Retinal ischemia and reperfusion causes capillary degeneration: similarities to diabetes. Invest Ophthalmol Vis Sci 48:361–367

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by OTKA K72592, CNK78480; F67830, T73044, ETT278-04/2009, 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, Funding Program for Next Generation World-Leading Researchers and Momentum Program of the Hungarian Academy of Sciences. SROP 4.2.1.B-10/2/KONV-2010-0002.

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Authors and Affiliations

  1. Departments of Experimental Zoology and Neurobiology, University of Pecs, Pecs, Hungary

    K. Szabadfi & R. Gabriel

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

    T. Atlasz

  3. Department of Anatomy, PTE-MTA “Lendulet” PACAP Research Team, University of Pecs, Szigeti U 12, Pecs, 7624, Hungary

    P. Kiss, B. Danyadi, A. Tamas & D. Reglodi

  4. Departments of Pharmacology and Pharmacotherapy, University of Pecs, Pecs, Hungary

    Zs. Helyes

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

    H. Hashimoto, N. Shintani & A. Baba

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

    H. Hashimoto

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

    H. Hashimoto

  8. Department of Medical Chemistry, University of Szeged, Osaka, Hungary

    G. Toth

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  1. K. Szabadfi
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  2. T. Atlasz
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  7. H. Hashimoto
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  8. N. Shintani
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  9. A. Baba
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  10. G. Toth
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  11. R. Gabriel
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  12. D. Reglodi
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Correspondence to D. Reglodi.

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Szabadfi, K., Atlasz, T., Kiss, P. et al. Mice Deficient in Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) are More Susceptible to Retinal Ischemic Injury In Vivo. Neurotox Res 21, 41–48 (2012). https://doi.org/10.1007/s12640-011-9254-y

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  • DOI: https://doi.org/10.1007/s12640-011-9254-y

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