scholarly journals Excitotoxic Insults Lead to Peroxiredoxin Hyperoxidation

2009 ◽  
Vol 2 (2) ◽  
pp. 110-113 ◽  
Author(s):  
Frédéric Léveillé ◽  
Francesc X. Soriano ◽  
Sofia Papadia ◽  
Giles E. Hardingham
Keyword(s):  
Oxidative Stress ◽  
Nmda Receptor ◽  
Response Curve ◽  
Synaptic Activity ◽  
Receptor Activity ◽  
Antioxidant Defenses ◽  
Enzymatic System ◽  
System A ◽  
Highly Sensitive ◽  
Toxic Concentrations

Post-mitotic neurons must have strong antioxidant defenses to survive the lifespan of the organism. We recently showed that neuronal antioxidant defenses are boosted by synaptic activity. Elevated synaptic activity, acting via the N-methyl-D-aspartate (NMDA) receptor, enhances thioredoxin activity, facilitates the reduction of hyperoxidized peroxiredoxins, and promotes resistance to oxidative stress. In contrast, blockade of spontaneous synaptic NMDA receptor activity renders neurons highly sensitive to hyperoxidation of peroxiredoxins by oxidative insults. These NMDA receptor-dependent effects are mediated in part by a coordinated program of gene expression changes centered on the thioredoxin-peroxiredoxin system, a thiol-based enzymatic system which is an important reducer of oxidative stressors such as hydroperoxides. We show here that while too little glutamatergic activity can render neurons vulnerable to peroxiredoxin hyperoxidation, so can too much. Exposure of neurons to toxic concentrations of glutamate, activating both synaptic and extrasynaptic NMDA receptors, acutely induces peroxiredoxin hyperoxidation. Thus, the effect of NMDA receptor activity on the activity of neuronal peroxiredoxins follows the classical U-shaped dose response curve.

Alteration of Energy Metabolism and Antioxidative Processing in the Hippocampus of Rats Reared in Long-Term Environmental Enrichment

2016 ◽  
Vol 38 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Hee Kang ◽  
Dong-Hee Choi ◽  
Su-Kang Kim ◽  
Jongmin Lee ◽  
Youn-Jung Kim
Keyword(s):  
Oxidative Stress ◽  
Energy Metabolism ◽  
Protein Expression ◽  
Environmental Enrichment ◽  
Synaptic Activity ◽  
Antioxidant Defenses ◽  
Laboratory Animals ◽  
Oxidative Stress Marker ◽  
Altered Expression

Environmental enrichment (EE) is a typical experimental method that promotes levels of novelty and complexity that enhance experience-dependent neuroplasticity and cognitive behavior function in laboratory animals. Early EE is associated with resilience in the face of later-life challenges. Since increased synaptic activity enhances endogenous neuronal antioxidant defenses, we hypothesized that long-term EE beginning at an early stage may alter the levels of oxidative stress. We investigated global protein expression and oxidative stress in hippocampal proteins from rats nurtured for a 6-month EE beginning in the prenatal period. The analysis of protein expression was carried out using 2-dimensional gel electrophoresis with matrix-associated laser desorption ionization time-of-flight mass spectrometry. Proteins with altered expression were involved in energy metabolism (phosphoglycerate mutase 1, α-enolase isoform 1, adenylate kinase 1, and triose phosphate isomerase) and antioxidant enzymes (superoxide dismutase 1, glutathione S-transferase ω type 1, peroxiredoxin 5, DJ-1, and glial maturation factor β). Using Western blot assays, some of the proteins with altered expression and NADPH oxidase 2 were confirmed to be decreased. Further confirmation was demonstrated with attenuated expression of 7,8-dihydro-8-oxo-deoxyguanine, a DNA oxidative stress marker, in the hippocampus of EE group rats. Our data demonstrate that a long-term EE program beginning in the prenatal and early postnatal phase of development modulates energy metabolism and reduced oxidant stress possibly through enhanced synaptic activity. We provide evidence that EE can be developed as a tool to protect the brain from oxidative stress-induced injury.

scholarly journals Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses

2008 ◽  
Vol 11 (4) ◽  
pp. 476-487 ◽  
Author(s):  
Sofia Papadia ◽  
Francesc X Soriano ◽  
Frédéric Léveillé ◽  
Marc-Andre Martel ◽  
Kelly A Dakin ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Receptor Activity ◽  
Antioxidant Defenses

scholarly journals Glutamate-induced RNA localization and translation in neurons

2016 ◽  
Vol 113 (44) ◽  
pp. E6877-E6886 ◽  
Author(s):  
Young J. Yoon ◽  
Bin Wu ◽  
Adina R. Buxbaum ◽  
Sulagna Das ◽  
Albert Tsai ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Dendritic Spines ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Localization ◽  
Synaptic Activity ◽  
Receptor Activity ◽  
Ideal System ◽  
Intracellular Compartments ◽  
Mrna Trafficking

Localization of mRNA is required for protein synthesis to occur within discrete intracellular compartments. Neurons represent an ideal system for studying the precision of mRNA trafficking because of their polarized structure and the need for synapse-specific targeting. To investigate this targeting, we derived a quantitative and analytical approach. Dendritic spines were stimulated by glutamate uncaging at a diffraction-limited spot, and the localization of single β-actin mRNAs was measured in space and time. Localization required NMDA receptor activity, a dynamic actin cytoskeleton, and the transacting RNA-binding protein, Zipcode-binding protein 1 (ZBP1). The ability of the mRNA to direct newly synthesized proteins to the site of localization was evaluated using a Halo-actin reporter so that RNA and protein were detected simultaneously. Newly synthesized Halo-actin was enriched at the site of stimulation, required NMDA receptor activity, and localized preferentially at the periphery of spines. This work demonstrates that synaptic activity can induce mRNA localization and local translation of β-actin where the new actin participates in stabilizing the expanding synapse in dendritic spines.

scholarly journals Synaptic NMDA receptor activity is coupled to the transcriptional control of the glutathione system

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Paul S. Baxter ◽  
Karen F.S. Bell ◽  
Philip Hasel ◽  
Angela M. Kaindl ◽  
Michael Fricker ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Transcriptional Control ◽  
Redox Balance ◽  
Synaptic Activity ◽  
Antioxidant Defenses ◽  
Glutathione System ◽  
Active Neuron ◽  
Glutathione Biosynthesis ◽  
The Face ◽  
Dependent Cell

Abstract How the brain’s antioxidant defenses adapt to changing demand is incompletely understood. Here we show that synaptic activity is coupled, via the NMDA receptor (NMDAR), to control of the glutathione antioxidant system. This tunes antioxidant capacity to reflect the elevated needs of an active neuron, guards against future increased demand and maintains redox balance in the brain. This control is mediated via a programme of gene expression changes that boosts the synthesis, recycling and utilization of glutathione, facilitating ROS detoxification and preventing Puma-dependent neuronal apoptosis. Of particular importance to the developing brain is the direct NMDAR-dependent transcriptional control of glutathione biosynthesis, disruption of which can lead to degeneration. Notably, these activity-dependent cell-autonomous mechanisms were found to cooperate with non-cell-autonomous Nrf2-driven support from astrocytes to maintain neuronal GSH levels in the face of oxidative insults. Thus, developmental NMDAR hypofunction and glutathione system deficits, separately implicated in several neurodevelopmental disorders, are mechanistically linked.

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