VIP, PACAP-38, BDNF and ADNP in NMDA-induced excitotoxicity in the rat retina
| Autor: | M. Kralinger, Barbara Teuchner, Josef Troger, Eduard Schmid, József Németh, G. F. Kieselbach, James A. Waschek, Reiner Fischer-Colbrie, Christian Humpel, Andreas Dimmer, Nikolaos E. Bechrakis, Albert Amberger |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty N-Methylaspartate Vasoactive intestinal peptide Radioimmunoassay Excitotoxicity Enzyme-Linked Immunosorbent Assay Nerve Tissue Proteins Endogeny Biology Real-Time Polymerase Chain Reaction medicine.disease_cause Neuroprotection Retina Rats Sprague-Dawley Neurotrophic factors Internal medicine Excitatory Amino Acid Agonists medicine Animals Flunarizine Brain-Derived Neurotrophic Factor Neuropeptides General Medicine Rats Up-Regulation Ophthalmology medicine.anatomical_structure Endocrinology nervous system Intravitreal Injections Pituitary Adenylate Cyclase-Activating Polypeptide NMDA receptor Oligopeptides hormones hormone substitutes and hormone antagonists Vasoactive Intestinal Peptide medicine.drug |
| Zdroj: | Acta Ophthalmologica. 89:670-675 |
| ISSN: | 1755-375X |
| Popis: | Purpose: To evaluate the effect of intravitreal injection of N-methyl-D-aspartate (NMDA) on brain-derived neurotrophic factor (BDNF), pituitary adenylate cyclase-activating peptide-38 (PACAP-38), vasoactive intestinal peptide (VIP) and the VIP-associated glial protein activity-dependent neuroprotective protein (ADNP) in the rat retina. These elements have well-documented neuroprotective properties and may thus be integrated in endogenous neuroprotective mechanisms in the retina which break down in NMDA excitotoxicity. Methods: A volume of 2 μl of 100 nmol NMDA was intravitreally injected into one eye of rats, the untreated eye served as a control. Time-dependent effects of NMDA on VIP, PACAP-38 and BDNF were detected by radioimmunoassay and ELISA, and the effect on the expression of VIP, PACAP-38 and ADNP was evaluated by quantitative RT-PCR 20 days after NMDA injection. Topical flunarizine served to find out whether the effect of NMDA is counteracted. Results: Compared to PACAP-38, VIP levels significantly decreased on days 1, 7, 14, 28 and 56 after NMDA injection indicating that VIPergic cells are more vulnerable than PACAP-38-expressing cells. The expression of VIP and ADNP but not of PACAP-38 was found to be reduced, and application of topical flunarizine counteracted the decrease of VIP. BDNF levels significantly increased after days 1 and 3. Conclusion: The early upregulation of BDNF seems to act neuroprotectively and leads to a delay of ganglion cell loss. Although there is no direct evidence, the decrease of VIP and ADNP – the consequence of the presence of NMDA receptors on these peptide-expressing cells – might contribute to the breakdown of endogenous neuroprotective mechanisms given that the decrease of the VIP-related ADNP runs in parallel with the decrease of VIP. Activating and maintaining these mechanisms must be the primary aim in the therapy of diseases with retinal neuronal degeneration. |
| Databáze: | OpenAIRE |
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