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Neuroprotective Effect of PACAP Against NMDA-Induced Retinal Damage in the Mouse

Neuroprotective Effect of PACAP Against NMDA-Induced Retinal Damage in the Mouse Retinal excitotoxicity is one of the major causes of retinal ganglion cell (RGC) death in glaucoma. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic peptide with potent neuroprotective activity; however, whether it exerts such an effect in the retina and the mechanism by which RGCs are protected is still not well understood. In this study, we examined the effect of exogenous and endogenous PACAP on RGC death induced by N-methyl-d-aspartate acid (NMDA). The vitreous body of anesthetized adult male mice (C57/BL6J) was injected with NMDA (40 nmol in a 2 μL saline solution). The number of RGCs decreased from days 1 to 7 after NMDA injection, and the number of dUTP end-labeling (TUNEL)-positive cells, an indicator of cell death, peaked at day 3. However, when PACAP38 (10−8, 10−10, 10−12, 10−14, or 10−16M) was co-administered with NMDA, the 10−10M dose resulted in significantly increased RGC survival at day 7, and a decrease in the number of TUNEL-positive RGCs at day 3. We next investigated the neuroprotective effect of endogenous PACAP using PACAP heterozygote(+/−) mice. Under normal circumstances, there was no significant difference in the number of RGCs in the PACAP(+/−) mice compared with their wild-type counterparts. However, the number of RGCs significantly decreased in the PACAP(+/−) mice 7 days after NMDA injection, relative to their wild-type counterparts. The number of TUNEL-positive RGCs peaked at day 1 in the PACAP(+/−) mice. These effects in the PACAP(+/−) mice were reversed by intravitreous injection of 10−10M PACAP38. This suggests that exogenous PACAP is able to counteract NMDA-induced toxicity, and that endogenous PACAP exerts a neuroprotective effect in the retina. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Molecular Neuroscience Springer Journals

Neuroprotective Effect of PACAP Against NMDA-Induced Retinal Damage in the Mouse

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Publisher
Springer Journals
Copyright
Copyright © 2010 by Springer Science+Business Media, LLC
Subject
Biomedicine; Neurology; Proteomics; Cell Biology; Neurochemistry; Neurosciences
ISSN
0895-8696
eISSN
1559-1166
DOI
10.1007/s12031-010-9434-x
pmid
20703829
Publisher site
See Article on Publisher Site

Abstract

Retinal excitotoxicity is one of the major causes of retinal ganglion cell (RGC) death in glaucoma. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic peptide with potent neuroprotective activity; however, whether it exerts such an effect in the retina and the mechanism by which RGCs are protected is still not well understood. In this study, we examined the effect of exogenous and endogenous PACAP on RGC death induced by N-methyl-d-aspartate acid (NMDA). The vitreous body of anesthetized adult male mice (C57/BL6J) was injected with NMDA (40 nmol in a 2 μL saline solution). The number of RGCs decreased from days 1 to 7 after NMDA injection, and the number of dUTP end-labeling (TUNEL)-positive cells, an indicator of cell death, peaked at day 3. However, when PACAP38 (10−8, 10−10, 10−12, 10−14, or 10−16M) was co-administered with NMDA, the 10−10M dose resulted in significantly increased RGC survival at day 7, and a decrease in the number of TUNEL-positive RGCs at day 3. We next investigated the neuroprotective effect of endogenous PACAP using PACAP heterozygote(+/−) mice. Under normal circumstances, there was no significant difference in the number of RGCs in the PACAP(+/−) mice compared with their wild-type counterparts. However, the number of RGCs significantly decreased in the PACAP(+/−) mice 7 days after NMDA injection, relative to their wild-type counterparts. The number of TUNEL-positive RGCs peaked at day 1 in the PACAP(+/−) mice. These effects in the PACAP(+/−) mice were reversed by intravitreous injection of 10−10M PACAP38. This suggests that exogenous PACAP is able to counteract NMDA-induced toxicity, and that endogenous PACAP exerts a neuroprotective effect in the retina.

Journal

Journal of Molecular Neuroscience – Springer Journals

Published: Aug 12, 2010

References

  • Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems
    Arimura, A
  • Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction
    Arimura, A; Shioda, S
  • Effects of pituitary adenylate cyclase activating polypeptide and its fragments on retinal degeneration induced by neonatal monosodium glutamate treatment
    Atlasz, T; Szabadfi, K; Reglodi, D
  • Evaluation of the protective effects of PACAP with cell-specific marlers in ischemia-induced retinal degeneration
    Atlasz, T; Szabadfi, K; Kiss, P
  • Vitreous body glutamate concentration in dogs with glaucoma
    Brooks, DE; Garcia, GA; Dreyer, EB; Zurakowski, D; Franco-Bourland, RE
  • Retinal TUNEL-positive cells and high glutamate levels in vitreous humor of mutant quail with a glaucoma-like disorder
    Dkhissi, O; Chanut, E; Wasowicz, M; Savoldelli, M; Nguyen-Legros, J; Minvielle, F; Versaux-Botteri, C
  • Experimental glutamatergic excitotoxicity in rabbit retinal ganglion cells: block by memantine
    Hare, WA; Wheeler, L
  • Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)
    Hashimoto, H; Shintani, N; Tanaka, K
  • Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death
    Kido, N; Tanihara, H; Honjo, M; Inatani, M; Tatsuno, T; Nakayama, C; Honda, Y
  • N-methyl-d-aspartate (NMDA)-induced apoptosis in rat retina
    Lam, TT; Abler, AS; Kwong, JM; Tso, MO
  • Signaling cascades involved in neuroprotection by subpicomolar pituitary adenylate cyclase-activating polypeptide 38
    Li, M; David, C; Kikuta, T; Somogyvari-Vigh, A; Arimura, A
  • PACAP38 modulates activity of NMDA receptors in cultured chick cortical neurons
    Liu, GJ; Madsen, BW
  • Orexin-1 receptor expression after global ischemia in mice
    Nakamachi, T; Endo, S; Ohtaki, H; Yin, L; Kenji, D; Kudo, Y; Funahashi, H; Matsuda, K; Shioda, S
  • Signaling involved in pituitary adenylate cyclase-activating polypeptide-stimulated ADNP expression
    Nakamachi, T; Li, M; Shioda, S; Arimura, A
  • Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6
    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
  • Ganglion cell death in glaucoma: pathology recapitulates ontogeny
    Quigley, HA
  • The neuroprotective effects of PACAP in monosodium glutamate-induced retinal lesion involve inhibition of proapoptotic signaling pathways
    Racz, B; Gallyas, F; Kiss, P
  • Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the PKA-BAD-14-3-3 signaling pathway in glutamate-induced retinal injury in neonatal rat
    Racz, B; Gallyas, F; Kiss, P
  • Distribution and ultrastructural localization of a receptor for pituitary adenylate cyclase activating polypeptide and its mRNA in the rat retina
    Seki, T; Shioda, S; Ogino, D; Nakai, Y; Arimura, A; Koide, R
  • Distribution and ultrastructural localization of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor in the rat retina
    Seki, T; Shioda, S; Nakai, Y; Arimura, A; Koide, R
  • Gene expression for PACAP receptor mRNA in the rat retina by in situ hybridization and in situ RT-PCR
    Seki, T; Izumi, S; Shioda, S; Zhou, CJ; Arimura, A; Koide, R
  • Electron microscopic observation of pituitary adenylate cyclase-activating polypeptide (PACAP)-containing neurons in the rat retina
    Seki, T; Shioda, S; Izumi, S; Arimura, A; Koide, R
  • Neuroprotective effect of PACAP against kainic acid-induced neurotoxicity in rat retina
    Seki, T; Nakatani, M; Taki, C; Shinohara, Y; Ozawa, M; Nishimura, S; Ito, H; Shioda, S
  • Suppression of ganglion cell death by PACAP following optic nerve transection in the rat
    Seki, T; Itoh, H; Nakamachi, T; Shioda, S
  • The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily
    Sherwood, NM; Krueckl, SL; McRory, JE
  • Neuroprotective action of endogenous PACAP in cultured rat cortical neurons
    Shintani, N; Suetake, S; Hashimoto, H; Koga, K; Kasai, A; Kawaguchi, C; Morita, Y; Hirose, M; Sakai, Y; Tomimoto, S; Matsuda, T; Baba, A
  • Pleiotropic functions of PACAP in the CNS: neuroprotection and neurodevelopment
    Shioda, S; Ohtaki, H; Nakamachi, T; Dohi, K; Watanabe, J; Nakajo, S; Arata, S; Kitamura, S; Okuda, H; Takenoya, F; Kitamura, Y
  • N-methyl-D-aspartate antagonists prevent kainate neurotoxicity in rat retinal ganglion cells in vitro
    Sucher, NJ; Aizenman, E; Lipton, SA
  • Effects of pituitary adenylate cyclase activating polypeptide in retinal degeneration induced by monosodium-glutamate
    Tamas, A; Gabriel, R; Racz, B; Denes, V; Kiss, P; Lubics, A; Lengvari, I; Reglodi, D
  • Prevention of ischemia-induced death of hippocampal neurons by pituitary adenylate cyclase activating polypeptide
    Uchida, D; Arimura, A; Somogyvari-Vigh, A; Shioda, S; Banks, WA
  • PACAP acts as a neurotrophic factor during histogenesis of the rat cerebellar cortex
    Vaudry, D; Gonzalez, BJ; Basille, M; Pamantung, TF; Fournier, A; Vaudry, H
  • Endogenous PACAP acts as a stress response peptide to protect cerebellar neurons from ethanol or oxidative insult
    Vaudry, D; Hamelink, C; Damadzic, R; Eskay, RL; Gonzalez, B; Eiden, LE
  • Pituitary adenylate cyclase-activating polypeptide (PACAP (1–38)) enhances N-methyl-d-aspartate receptor function and brain-derived neurotrophic factor expression via RACK1
    Yaka, R; He, DY; Phamluong, K; Ron, D

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