Oxidative stress mediated by NMDA, AMPA/KA channels in acute hippocampal slices: Neuroprotective effect of resveratrol

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• 作者：André ; Quincozes-Santos ; ^{andrequincozes@yahoo.com.br" class="auth_mail} ; Larissa Daniele Bobermin ; Ana Carolina Tramontina ; Krista Miné ; ia Wartchow ; Bá ; rbara Tagliari ; Diogo Onofre Souza ; Angela T.S. Wyse ; Carlos-Alberto Gonç ; alves
• 关键词：Resveratrol ; Glutamate toxicity ; Glutamate receptors ; Oxidative stress ; HO1
• 刊名：Toxicology in Vitro
• 出版年：June, 2014
• 年：2014
• 卷：28
• 期：4
• 页码：544-551
• 全文大小：485 K

文摘

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 Ca²⁺ 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 (螖唯_m), Na⁺K⁺-ATPase and glutamine synthetase (GS) activity. Resveratrol decreases intracellular ROS production, most likely by mechanisms involving NMDA, AMPA/KA, intracellular Ca²⁺ 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.