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Oxidative stress mediated by NMDA, AMPA/KA channels in acute hippocampal slices: neuroprotective effect of resveratrol.
Toxicol In Vitro. 2014 Jun; 28(4):544-51.TV

Abstract

Glutamate is the major excitatory neurotransmitter in the brain and over-stimulation of the glutamate receptors, NMDA, AMPA and kainate (KA), may cause neuronal death in epilepsy, seizures and neurodegenerative diseases. Mitochondria have critical cellular functions that influence neuronal excitability, such as regulation of Ca(2+) homeostasis and ATP production to maintain Na(+)K(+)-ATPase in the central nervous system (CNS). However, mitochondria are also the primary site of reactive oxygen species (ROS) production, and oxidative stress can induce cellular damage. Resveratrol, a polyphenol found in grapes and wines, presents antioxidant and neuroprotective effects on brain pathologies. This study sought to determine the neuroprotective effect of resveratrol against glutamate toxicity in acute hippocampal slices, using specific inhibitors of glutamate channels, and to investigate the targets of glutamate excitotoxicity, such as mitochondrial membrane potential (ΔΨ(m)), Na(+)K(+)-ATPase and glutamine synthetase (GS) activity. Resveratrol decreases intracellular ROS production, most likely by mechanisms involving NMDA, AMPA/KA, intracellular Ca(2+) and the heme oxygenase 1 (HO1) pathway, and prevents mitochondrial dysfunction and impairments in Na(+)K(+)-ATPase and GS activity after glutamate activation. Taken together, these results show that resveratrol may exhibit an important neuroprotective mechanism against neuropsychiatric disorders, focusing on mitochondrial bioenergetics and oxidative stress, as well as inhibitory effects on ionic channels.

Authors+Show Affiliations

Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: andrequincozes@yahoo.com.br.Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Pub Type(s)

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

Language

eng

PubMed ID

24412540

Citation

Quincozes-Santos, André, et al. "Oxidative Stress Mediated By NMDA, AMPA/KA Channels in Acute Hippocampal Slices: Neuroprotective Effect of Resveratrol." Toxicology in Vitro : an International Journal Published in Association With BIBRA, vol. 28, no. 4, 2014, pp. 544-51.
Quincozes-Santos A, Bobermin LD, Tramontina AC, et al. Oxidative stress mediated by NMDA, AMPA/KA channels in acute hippocampal slices: neuroprotective effect of resveratrol. Toxicol In Vitro. 2014;28(4):544-51.
Quincozes-Santos, A., Bobermin, L. D., Tramontina, A. C., Wartchow, K. M., Tagliari, B., Souza, D. O., Wyse, A. T., & Gonçalves, C. A. (2014). Oxidative stress mediated by NMDA, AMPA/KA channels in acute hippocampal slices: neuroprotective effect of resveratrol. Toxicology in Vitro : an International Journal Published in Association With BIBRA, 28(4), 544-51. https://doi.org/10.1016/j.tiv.2013.12.021
Quincozes-Santos A, et al. Oxidative Stress Mediated By NMDA, AMPA/KA Channels in Acute Hippocampal Slices: Neuroprotective Effect of Resveratrol. Toxicol In Vitro. 2014;28(4):544-51. PubMed PMID: 24412540.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative stress mediated by NMDA, AMPA/KA channels in acute hippocampal slices: neuroprotective effect of resveratrol. AU - Quincozes-Santos,André, AU - Bobermin,Larissa Daniele, AU - Tramontina,Ana Carolina, AU - Wartchow,Krista Minéia, AU - Tagliari,Bárbara, AU - Souza,Diogo Onofre, AU - Wyse,Angela T S, AU - Gonçalves,Carlos-Alberto, Y1 - 2014/01/08/ PY - 2013/10/27/received PY - 2013/12/19/revised PY - 2013/12/28/accepted PY - 2014/1/14/entrez PY - 2014/1/15/pubmed PY - 2015/6/30/medline KW - Glutamate receptors KW - Glutamate toxicity KW - HO1 KW - Oxidative stress KW - Resveratrol SP - 544 EP - 51 JF - Toxicology in vitro : an international journal published in association with BIBRA JO - Toxicol In Vitro VL - 28 IS - 4 N2 - Glutamate is the major excitatory neurotransmitter in the brain and over-stimulation of the glutamate receptors, NMDA, AMPA and kainate (KA), may cause neuronal death in epilepsy, seizures and neurodegenerative diseases. Mitochondria have critical cellular functions that influence neuronal excitability, such as regulation of Ca(2+) homeostasis and ATP production to maintain Na(+)K(+)-ATPase in the central nervous system (CNS). However, mitochondria are also the primary site of reactive oxygen species (ROS) production, and oxidative stress can induce cellular damage. Resveratrol, a polyphenol found in grapes and wines, presents antioxidant and neuroprotective effects on brain pathologies. This study sought to determine the neuroprotective effect of resveratrol against glutamate toxicity in acute hippocampal slices, using specific inhibitors of glutamate channels, and to investigate the targets of glutamate excitotoxicity, such as mitochondrial membrane potential (ΔΨ(m)), Na(+)K(+)-ATPase and glutamine synthetase (GS) activity. Resveratrol decreases intracellular ROS production, most likely by mechanisms involving NMDA, AMPA/KA, intracellular Ca(2+) and the heme oxygenase 1 (HO1) pathway, and prevents mitochondrial dysfunction and impairments in Na(+)K(+)-ATPase and GS activity after glutamate activation. Taken together, these results show that resveratrol may exhibit an important neuroprotective mechanism against neuropsychiatric disorders, focusing on mitochondrial bioenergetics and oxidative stress, as well as inhibitory effects on ionic channels. SN - 1879-3177 UR - https://www.unboundmedicine.com/medline/citation/24412540/Oxidative_stress_mediated_by_NMDA_AMPA/KA_channels_in_acute_hippocampal_slices:_neuroprotective_effect_of_resveratrol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0887-2333(14)00003-4 DB - PRIME DP - Unbound Medicine ER -