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Neurotoxicity Research

, Volume 8, Issue 3–4, pp 227–233 | Cite as

Degree of damage compensation by various pacap treatments in monosodium glutamate-induced retinal degeneration

  • Norbert Babai
  • Tamás Atlasz
  • Andrea Tamás
  • Dóra ReglodiEmail author
  • Gábor Tóth
  • Péter Kiss
  • Róbert Gábriel
Article

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to be neuroprotective in retinal ischemia and monosodium L-glutamate (MSG)-induced retinal degeneration. Here we describe how different MSG treatments (1x and 3x application) cause retinal damage and finally lead to the destruction of the entire inner retina and how PACAP attenuates this effect. Newborn rats from both sexes were injected subcutaneously with 2 mg/g bodyweight MSG on postnatal days 1, 5 and 9. The left eye was left intact while we injected 5 µl PACAP38 solution (100 pmol) into the vitreous of the right eye with a Hamilton syringe at the time of (i) the first, (ii) the first two or (iii) all three MSG injections. Histological analysis has shown that the above described MSG treatment caused the entire inner plexiform layer (IPL) to degenerate, and the inner nuclear (INL) and ganglion cell layers (GCL) seemed fused. One time PACAP38 treatment at the first MSG application did not change the degenerative capacity of MSG. However, if animals received PACAP38 into the vitreous of the eye at the first 2 or all 3 times, a substantial protective effect could be observed. The IPL remained well discernible, the INL retained 2–3 cell rows and the number of cells in the GCL was substantially higher than in the MSG-treated retinas, and was not significantly different from that observed in the control tissue. We conclude that (i) 2 or 3 times PACAP treatment attenuates retinal degeneration; (ii) one PACAP treatment does not provide protection against repeated excitotoxic insults, and (iii) repeated application of PACAP under these experimental conditions may lead to a primed state in which further neurotoxic insults are ineffective.

Keywords

PACAP Glutamate Retina Degeneration Excitotoxicity Neurotoxicity Neuroprotection 

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References

  1. Bagnoli P, M Dal Monte and G Casini (2003) Expression of neuro-peptides and their receptors in the developing retina of mammals.Histol. Histopathol. 18, 1219–1242.PubMedGoogle Scholar
  2. Chambille I and J Serviere (1993) Neurotoxic effect of neonatal injections of monosodium L-glutamate (L-MSG) in the retinal ganglion cell layer of the golden hamster: anatomical and functional consequences on the circadian system.J. Comp. Neurol. 338, 67–82.PubMedCrossRefGoogle Scholar
  3. Chen Q, JW Olney, PD Lukasiewicz, T Almli and C Romano (1998) Fenamates protect against ischemic and excitotoxic injury in chick embryo retina.Neurosci. Lett. 242, 163–166.PubMedCrossRefGoogle Scholar
  4. Danysz W and CG Parsons (2002) Neuroprotective potential of ionotropic glutamate receptor antagonists.Neurotoxicity Res. 4, 119–126.CrossRefGoogle Scholar
  5. Frechilla D, A Garcia-Osta, S Palacios, E Cenarruzabeitia and J Del Rio (2001) BDNF mediates the neuroprotective effect of PACAP38 on rat cortical neurons.Neuroreport 12, 919–923.PubMedCrossRefGoogle Scholar
  6. Gábriel R and P Witkovsky (1998) Cholinergic, but not the rod pathway-related glycinergic (AII), amacrine cells contain cal-retinin in the rat retina.Neurosci. Lett. 247, 179–182.PubMedCrossRefGoogle Scholar
  7. Gábriel R, BS Zhu and C Stranicky (1993) Synaptic contacts of serotonin-like immunoreactive and 5,7-dihydroxytryptamine accumulating neurons in the anuran retina.Neuroscience 54, 1103–1114.PubMedCrossRefGoogle Scholar
  8. Hamano K, H Kiyama, PC Emson, R Manabe, M Nakauchi and M Tohyama (1990) Localization of two calcium-binding proteins, calbindin (28 kDa) and parvalbumin (12 kDa) in the vertebrate retina.J. Comp. Neurol. 302, 417–424.PubMedCrossRefGoogle Scholar
  9. Izumi S, T Seki, S Shioda, CJ Zhou, A Arimura and R Koide (2000) Ultrastructural localization of PACAP immunoreactivity in the rat retina.Ann. NYAcad. Sci. 921, 317–320.Google Scholar
  10. Jozsa R, A Somogyvari-Vigh, D Reglodi, T Hollosy and A Arimura (2001) Distribution and daily variations of PACAP in the chicken brain.Peptides 22, 1371–1377.PubMedCrossRefGoogle Scholar
  11. Koves K, O Kantor, V Vereczki, M Kausz, A Nemeskeri, K Fogel, A Kiss, TJ Gorcs, G Szeiffert and A Atrimura (2000) PACAP and VIP in the photoneuroendocrine system. From the retina to the pituitary gland.Ann. NYAcad. Sci. 921, 321–326.Google Scholar
  12. Kubrusly RC, MC da Cunha, RA Reis, H Soares, AL Ventura, E Kurtenbach, MC de Mello and FC de Mello (2005) Expression of functional receptors and transmitter enzymes in cultured Muller cells.Brain Res. 1038, 141–149.PubMedCrossRefGoogle Scholar
  13. Mathieu M, M Ciarlo, N Trucco, F Griffero, G Damonte, A Salis and M Vallarino (2004) Pituitary adenylate cyclase activating polypeptide in the brain, spinal cord and sensory organs of the zebrafish,Danio rerio, during development.Dev. Brain Res. 151, 169–185.CrossRefGoogle Scholar
  14. Morio H, I Tatsuno, A Hirai, Y Tamura and Y Saitoh (1996) Pituitary adenylate cyclase activating polypeptide protects rat-cultured cortical neurons from glutamate-induced cytotoxicity.Brain Res. 741, 82–88.PubMedCrossRefGoogle Scholar
  15. Nilsson SF (1994) PACAP-27 and PACAP-38: vascular effects in the eye and some other tissues in the rabbit.Eur. J. Pharmacol. 253, 17–25.PubMedCrossRefGoogle Scholar
  16. Nilsson SF, P De Neef, P Robberecht and J Christophe (1994) Characterization of ocular receptors for pituitary adenylate cyclase activating polypeptide (PACAP) and their coupling to adenylate cyclase.Exp. Eye Res. 58, 459–467.PubMedCrossRefGoogle Scholar
  17. Olianas MC, A Ingianni, V Sogos and P Onali (1997) Expression of pituitary adenylate cyclase activating polypeptide (PACAP) receptors and PACAP in human fetal retina.J. Neurochem. 69, 1213–1218.PubMedGoogle Scholar
  18. Onali P and MC Olianas (1994) PACAP is a potent and highly effective stimulator of adenylyl cyclase activity in the retinas of different mammalian species.Brain Res. 641, 132–134.PubMedCrossRefGoogle Scholar
  19. Osborne NN, M Ugarte, M Chao, G Chidlow, JH Bae, JP Wood and MS Nash (1999) Neuroprotection in relation to retinal ischemia and relevance to glaucoma.Surv. Ophtalmol. 43 Suppl. 1, S102-S128.CrossRefGoogle Scholar
  20. Osborne NN, RJ Casson, JP Wood, G Chidlow, M Graham and J Melena (2004) Retinal ischemia: mechanisms of damage and potential therapeutic strategies.Prog. Retin. Eye Res. 23, 91–147.PubMedCrossRefGoogle Scholar
  21. Paicone LR, MJ Szego, S Ikeda, PM Nishima and RR McInnes (2003) Progress toward understandig the genetic and biochemical mechanisms of inherited photoreceptor degenerations.Ann. Rev. Neurosci. 26, 657–700.CrossRefGoogle Scholar
  22. Pedersen V and WJ Schmidt (2000) The neuroprotective properties of glutamate antagonists and antiglutamatergic drugs.Neurotoxicity Res. 2, 179–204.Google Scholar
  23. Rabl K, D Reglodi, T Banvolgyi, A Somogyvari-Vigh, I Lengvari, R Gabriel and A Arimura (2002) PACAP inhibits anoxia-induced changes in physiological responses in horizontal cells in the turtle retina.Regul. Pept. 109, 71–74.PubMedCrossRefGoogle Scholar
  24. Reglodi D, A Tamas, A Somogyvari-Vigh, Z Szanto, E Kertes, L Lenard, A Arimura and I Lengvari (2002) Effects of pretreatment with PACAP on the infarct size and functional outcome in rat permanent focal cerebral ischemia.Peptides 23, 2227–2234.PubMedCrossRefGoogle Scholar
  25. Romano C, MT Price and JW Olney (1995) Delayed excitotoxic neurodegeneration induced by excitatory amino acid agonists in isolated retina.J. Neurochem. 65, 59–67.PubMedGoogle Scholar
  26. Samuelsson-Almen M and SF Nilsson (1999) Pituitary adenylate cyclase activating polypeptide- and VIP-induced activation of adenylate cyclase in the porcine non-pigmented ciliary epithelium: effects of antagonists.J. Ocul. Pharmacol. Ther. 15, 389–400.PubMedCrossRefGoogle Scholar
  27. Seki T, S Shioda, D Ogino Y Nakai, A Arimura and R Koide (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.PubMedCrossRefGoogle Scholar
  28. Seki T, S Shioda, S Izumi, A Arimura and R Koide (2000) Electron microscopic observation of pituitary adenylate cyclase activating polypeptide (PACAP)-containing neurons in the rat retina.Peptides 21, 109–113.PubMedCrossRefGoogle Scholar
  29. Seki T, S Izumi, S Shioda and A Arimura (2003) Pituitary adenylate cyclase activating polypeptide (PACAP) protects against ganglion cell death after cutting of optic nerve in the rat retina.Regul. Pept. 115, 55.Google Scholar
  30. Shoge K, HK Mishima, T Saitoh, K Ishihara, Y Tamura, H Shiomi and M Sasa (1998) Protective effects of vasoactive intestinal peptide against delayed glutamate neurotoxicity in cultured retina.Brain Res. 809, 127–136.PubMedCrossRefGoogle Scholar
  31. Shoge K, HK Mishima, T Saitoh, K Ishihara, Y Tamura, H Shiomi, and M Sasa (1999) Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons.Brain Res. 839, 66–73.PubMedCrossRefGoogle Scholar
  32. Silveira MS, MR Costa, M Bozza and R Linden (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.PubMedCrossRefGoogle Scholar
  33. Smythies J (1999) The neurotoxicity of glutamate, domapine, iron and reactive oxygen species: functional interrelationships in health and disease: a review - discussion.Neurotoxicity Res. 1, 27–39.Google Scholar
  34. Somogyvari-Vigh A and D Reglodi (2004) Pituitary adenylate cyclase activating polypeptide: a potential neuroprotective peptide. Review.Curr. Pharm. Des. 10, 2861–2889.PubMedCrossRefGoogle Scholar
  35. Sucher NJ, SA Lipton and EB Dreyer (1997) Molecular basis of glutamate toxicity in retinal ganglion cells.Vision Res. 37, 3483–3493.PubMedCrossRefGoogle Scholar
  36. Sun Q, VEC Ooi, and SO Chan (2001)N-methyl-D-aspartate-induced excitotoxicity in adult rat retina is antagonized by single systemic injection of MK-801.Exp. Brain Res. 138, 37–45.PubMedCrossRefGoogle Scholar
  37. Tamas A, R Gabriel, B Racz, V Denes, P Kiss, A Lubics, I Lengvari and D Reglodi (2004) Effects of pituitary adenylate cyclase activating polypeptide in retinal degeneration induced by mono-sodium-glutamate.Neurosci. Lett. 372, 110–113.PubMedCrossRefGoogle Scholar
  38. Thoreson WB and P Witkovsky (1999) Glutamate receptors and circuits in the vertebrate retina.Prog. Retinal Res. 18, 765–810.CrossRefGoogle Scholar
  39. Toriu N, A Akaibe, H Yasuyoshi, S Zhang, S Kashii, Y Honda, M Shimazawa and H Hara (2000) Lomerizine, a Ca2+ channel blocker, reduces glutamate-induced neurotoxicity and ischemia/ reperfusion damage in rat retina.Exp. Eye Res. 70, 475–484.PubMedCrossRefGoogle Scholar
  40. Tuncel N, H Basmak, K Uzuner, M Tuncel, G Altiokka, V Zaimoglu, A Ozer and F Gurer (1996) Protection of rat retina from ischemia-reperfusion injury by vasoactive intestinal peptide (VIP): the effect of VIP on lipid peroxidation and antioxidant enzyme activity of retina and choroid.Ann. NY Acad. Sci. 805, 489–498.PubMedCrossRefGoogle Scholar
  41. van Rijn CM, E Marani and WJ Rietveld (1986) The neurotoxic effect of monosodium glutamate (MSG) on the retinal ganglion cells of the albino rat.Histol. Histopathol. 1, 291–295.PubMedGoogle Scholar
  42. Vaudry D, BJ Gonzalez, M Basille, Y Anouar, A Fournier and H Vaudry (1998) Pituitary adenylate cyclase activating polypeptide stimulates both c-fos gene expression and cell survival in rat cerebellar granule neurons through activation of the protein kinase Apathway.Neuroscience 84, 801–812.PubMedCrossRefGoogle Scholar
  43. Vidal-Sanz M, M Lafuente, P Sobrado-Calvo, I Selles-Navarro, E Rodriguez, S Mayor-Torroglosa and MP Villegas-Perez (2000) Death and neuroprotection of retinal ganglion cells after different types of injury.Neurotoxicity Res. 2, 215–227.Google Scholar
  44. Villani L, A Beraudi, A Guiliani and A Poli (2001) MPTP-induced apoptosis in the retina of goldfish.Neurotoxicity Res. 3, 255–257.CrossRefGoogle Scholar
  45. Wang YZ, P Alm and R Hakanson (1995) Distribution and effects of pituitary adenylate cyclase activating peptide in the rabbit eye.Neuroscience 69, 297–308.PubMedCrossRefGoogle Scholar
  46. Waschek JA (2002) Multiple actions of pituitary adenylyl cyclase activating peptide in nervous system development and regeneration.Dev. Neurosci. 24, 14–23.PubMedCrossRefGoogle Scholar
  47. Wassle H, U Grunert and J Rohrenbeck (1993) Immunocytochemical staining of AII amacrine cells in the rat retina with antibodies against parvalbumin.J. Comp. Neurol. 322, 407–420.CrossRefGoogle Scholar
  48. Yoshitomi T, K Yamaji, H Ishikawa and Y Ohnishi (2002) Effect of pituitary adenylate cyclase activating peptide on isolated rabbit iris sphincter and dilator muscles.Invest. Ophtalmol. Vis. Sci. 43, 780–783.Google Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Norbert Babai
    • 1
  • Tamás Atlasz
    • 1
  • Andrea Tamás
    • 2
  • Dóra Reglodi
    • 2
    • 3
    Email author
  • Gábor Tóth
    • 4
  • Péter Kiss
    • 2
  • Róbert Gábriel
    • 1
    • 5
  1. 1.Department of General Zoology and NeurobiologyPécs UniversityHungary
  2. 2.Department of AnatomyPécsUniversity Medical FacultyHungary
  3. 3.Neurohumoral Regulations Research Group of the Hungarian Academy of SciencesHungary
  4. 4.Department of Medical ChemistryUniversity of SzegedHungary
  5. 5.Adaptational Biology Research Group of the Hungarian Academy of SciencesHungary

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