Glutathione depletion: Starting point of brain metabolic stress, neuroinflammation and cognitive impairment in rats.

Abstract

Glutathione provides protection from oxidative stress-induced damage through the reduction of reactive oxygen species for the maintenance of oxidant homeostasis. Our purpose was to test the effects of depleting tissue GSH by buthionine sulfoximine on brain oxidative metabolism and cognitive performance in rats. Glutathione depletion induced a compensatory response on antioxidant enzymes and increase of cell damage indicators in all the examined cerebral areas at 24h. The effect of GSH depletion on spatial memory recorded at 24h post-surgery showed significant differences between experimental groups for the escape latency to the platform and percentage of total swim distance spending in the target quadrant. The acquisition of a new spatial condition 24h after GSH depletion revealed differences between experimental groups for latencies, swim distance, swim distance in the target quadrant and percentage of total swim distance spending in the target quadrant. The ability of BSO treated group to maintain a restraining behavior was significantly smaller compared with control group. We founded significant correlation among variables of the behavioral studies and oxidative stress indicators. In conclusion, our model shows how increased ROS production by transitory glutathione depletion constitutes the primary cause to neuronal metabolic stress with alterations in synaptic signaling and cognitive deficits.

• Authors: Maria Elena González-Fraguela, Lisette Blanco, Caridad Ivette Fernández, Lourdes Lorigados, Teresa Serrano, Jessica López Fernández
• Journal: Brain research bulletin (Brain Res Bull) Vol. 137 Pg. 120-131 (03 2018) ISSN: 1873-2747 [Electronic] United States
• PMID: 29183693 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• Buthionine Sulfoximine
• Glutathione

Topics

• Animals
• Avoidance Learning (physiology)
• Brain (metabolism)
• Brain Diseases (metabolism)
• Buthionine Sulfoximine
• Cognitive Dysfunction (metabolism)
• Disease Models, Animal
• Glutathione (deficiency)
• Inflammation (metabolism)
• Male
• Maze Learning (physiology)
• Oxidative Stress (physiology)
• Random Allocation
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Spatial Memory (physiology)
• Tumor Necrosis Factor-alpha (metabolism)