Chronic Hypoxia Potentiates Age-Related Oxidative Imbalance in Brain Vessels and Synaptosomes

Cristina      Carvalho; Maria      S. Santos; Ines      Baldeiras; Catarina      R. Oliveira; Raquel      Seica; Paula      I. Moreira

Abstract

This study was aimed to evaluate and compare the effect of chronic hypoxia and aging in the oxidative status of brain vessels and synaptosomes. For this purpose we isolated brain vessels and synaptosomes from 3- and 12-month-old rats subjected to chronic hypoxia (10% O2 for 7 days) or normoxia (21% O2). Several parameters were evaluated: mitochondrial aconitase activity, hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels and enzymatic [superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR)] and non-enzymatic [glutathione (GSH), glutathione disulfide (GSSG) and vitamin E] antioxidant defences. Concerning brain vessels, we observed an age-dependent increase in MDA levels and SOD, catalase, GR and GPx activities. In vessels isolated from young animals, chronic hypoxia induced an increase in H2O2, GSSG and vitamin E levels and CuZnSOD and catalase activities and a decrease in GSH levels. In mature animals, hypoxia induced a decrease in GSH/GSSG ratio, vitamin E levels and mitochondrial aconitase, MnSOD and GR activities and an increase in H2O2 levels and CuZnSOD and catalase activities. Concerning synaptosomes we observed an age-dependent increase in MDA levels, CuZnSOD and GPx activities and a decrease in MnSOD activity. In synaptosomes from young animals, chronic hypoxia induced a decrease in mitochondrial aconitase activity and GSH levels and an increase in CuZnSOD activity and GSSG levels. In synaptosomes from mature animals, hypoxia induced a decrease in mitochondrial aconitase activity, GSH/GSSG ratio, GSH and vitamin E levels and an increase in GSSG levels. Our results show that chronic hypoxia promotes and potentiates age-dependent oxidative imbalance predisposing to neurodegeneration. Further, synaptosomes and brain vessels are differently affected by aging and chronic hypoxia supporting the idea of the existence of tissue-specific susceptibilities.

Keywords: Aging, brain vessels, chronic hypoxia, neurodegeneration, oxidative stress, synaptosomes, calcium homeostasis, Alzheimer's disease, H2O2, MDA, SOD, GR, GSSG, FELASA, (CBC) Analyses, (Tg) Levels, (CK) Levels, Vitamin E, Mitochondrial aconitase activity, NBT, protein kinase C, CRP, RBC, HGB, RDW, Antioxidant, ROS, Lipid Peroxidation, NF-κB, (AP)-1, Catalase, CuZnSOD, NADPH