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Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate.
Cell Death Dis. 2013 May 16; 4:e636.CD

Abstract

It has been claimed that glutamate excitotoxicity might have a role in the pathogenesis of several retinal degenerative diseases, including glaucoma and diabetic retinopathy. Neuropeptide Y (NPY) has neuroprotective properties against excitotoxicity in the hippocampus, through the activation of Y1, Y2 and/or Y5 receptors. The principal objective of this study is to investigate the potential protective role of NPY against glutamate-induced toxicity in rat retinal cells (in vitro and in an animal model), unraveling the NPY receptors and intracellular mechanisms involved. Rat retinal neural cell cultures were prepared from newborn Wistar rats (P3-P5) and exposed to glutamate (500 μM) for 24 h. Necrotic cell death was evaluated by propidium iodide (PI) assay and apoptotic cell death using TUNEL and caspase-3 assays. The cell types present in culture were identified by immunocytochemistry. The involvement of NPY receptors was assessed using selective agonists and antagonists. Pre-treatment of cells with NPY (100 nM) inhibited both necrotic cell death (PI-positive cells) and apoptotic cell death (TUNEL-positive cells and caspase 3-positive cells) triggered by glutamate, with the neurons being the cells most strongly affected. The activation of NPY Y2, Y4 and Y5 receptors inhibited necrotic cell death, while apoptotic cell death was only prevented by the activation of NPY Y5 receptor. Moreover, NPY neuroprotective effect was mediated by the activation of PKA and p38K. In the animal model, NPY (2.35 nmol) was intravitreally injected 2 h before glutamate (500 nmol) injection into the vitreous. The protective role of NPY was assessed 24 h after glutamate (or saline) injection by TUNEL assay and Brn3a (marker of ganglion cells) immunohistochemistry. NPY inhibited the increase in the number of TUNEL-positive cells and the decrease in the number of Brn3a-positive cells induced by glutamate. In conclusion, NPY and NPY receptors can be considered potential targets to treat retinal degenerative diseases, such as glaucoma and diabetic retinopathy.

Authors+Show Affiliations

CNC - Center for Neuroscience and Cell Biology, University of Coimbra; Largo Marquês de Pombal, Coimbra, Portugal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23681231

Citation

Santos-Carvalho, A, et al. "Neuropeptide Y Receptors Activation Protects Rat Retinal Neural Cells Against Necrotic and Apoptotic Cell Death Induced By Glutamate." Cell Death & Disease, vol. 4, 2013, pp. e636.
Santos-Carvalho A, Elvas F, Alvaro AR, et al. Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate. Cell Death Dis. 2013;4:e636.
Santos-Carvalho, A., Elvas, F., Alvaro, A. R., Ambrósio, A. F., & Cavadas, C. (2013). Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate. Cell Death & Disease, 4, e636. https://doi.org/10.1038/cddis.2013.160
Santos-Carvalho A, et al. Neuropeptide Y Receptors Activation Protects Rat Retinal Neural Cells Against Necrotic and Apoptotic Cell Death Induced By Glutamate. Cell Death Dis. 2013 May 16;4:e636. PubMed PMID: 23681231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate. AU - Santos-Carvalho,A, AU - Elvas,F, AU - Alvaro,A R, AU - Ambrósio,A F, AU - Cavadas,C, Y1 - 2013/05/16/ PY - 2013/5/18/entrez PY - 2013/5/18/pubmed PY - 2013/10/24/medline SP - e636 EP - e636 JF - Cell death & disease JO - Cell Death Dis VL - 4 N2 - It has been claimed that glutamate excitotoxicity might have a role in the pathogenesis of several retinal degenerative diseases, including glaucoma and diabetic retinopathy. Neuropeptide Y (NPY) has neuroprotective properties against excitotoxicity in the hippocampus, through the activation of Y1, Y2 and/or Y5 receptors. The principal objective of this study is to investigate the potential protective role of NPY against glutamate-induced toxicity in rat retinal cells (in vitro and in an animal model), unraveling the NPY receptors and intracellular mechanisms involved. Rat retinal neural cell cultures were prepared from newborn Wistar rats (P3-P5) and exposed to glutamate (500 μM) for 24 h. Necrotic cell death was evaluated by propidium iodide (PI) assay and apoptotic cell death using TUNEL and caspase-3 assays. The cell types present in culture were identified by immunocytochemistry. The involvement of NPY receptors was assessed using selective agonists and antagonists. Pre-treatment of cells with NPY (100 nM) inhibited both necrotic cell death (PI-positive cells) and apoptotic cell death (TUNEL-positive cells and caspase 3-positive cells) triggered by glutamate, with the neurons being the cells most strongly affected. The activation of NPY Y2, Y4 and Y5 receptors inhibited necrotic cell death, while apoptotic cell death was only prevented by the activation of NPY Y5 receptor. Moreover, NPY neuroprotective effect was mediated by the activation of PKA and p38K. In the animal model, NPY (2.35 nmol) was intravitreally injected 2 h before glutamate (500 nmol) injection into the vitreous. The protective role of NPY was assessed 24 h after glutamate (or saline) injection by TUNEL assay and Brn3a (marker of ganglion cells) immunohistochemistry. NPY inhibited the increase in the number of TUNEL-positive cells and the decrease in the number of Brn3a-positive cells induced by glutamate. In conclusion, NPY and NPY receptors can be considered potential targets to treat retinal degenerative diseases, such as glaucoma and diabetic retinopathy. SN - 2041-4889 UR - https://www.unboundmedicine.com/medline/citation/23681231/Neuropeptide_Y_receptors_activation_protects_rat_retinal_neural_cells_against_necrotic_and_apoptotic_cell_death_induced_by_glutamate_ L2 - http://dx.doi.org/10.1038/cddis.2013.160 DB - PRIME DP - Unbound Medicine ER -