The influence of reactive oxygen species on the central nervous system

Abstract

Oxidative stress can be defined as a rise of oxidative potential or decrease of antioxidant status. Oxidative stress is caused by reactive oxygen species (ROS) which are produced by one-electron reduction of oxygen in the electron transport chain, as well as many other reactions. Effects of ROS can result in cellular membrane damage, structural and functional changes in enzymatic and non-enzymatic proteins, and damage to the DNA structure. Excessive generation of free radicals, decrease of enzymatic antioxidant activity, and/or reducing agents are considered as the main causes of oxidative stress. Since the brain contains a large amount of polyunsaturated fatty acids, consumes up to 20% of oxygen used by the whole body, and shows low antioxidant activity, it seems to be especially vulnerable to oxidative stress. Numerous data show the significant role of oxidative stress in pathogenesis of many neurodegenerative diseases.

The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

“…The same is caused by its high demand for oxygen (approximately 20% of the organism's total oxygen intake) and high content of lipids and transition metals (e.g., copper and iron), as well as relatively low levels of antioxidative enzymes [32]. Approximately 5% of the oxygen used in the mitochondria, peroxisomes, and microsomes of the respiratory chain is converted into ROS [7]. Due to their shape, neurons are characterized by a very disadvantageous ratio of surface area to volume, while cell membranes are the most susceptible to the effects of ROS as they can suffer changes to, e.g., their fluidity as a result of lipid peroxidation and oxidation of the thiol groups in membrane proteins [7].…”

“…A significantly increased concentration of Fe and Cu was observed in brain tissue collected post-mortem from the brains of HD patients, as well as in the cerebral tissues of R6/2 mice and in the Drosophila HD model [21]. Increased accumulations of Fe were also observed in the ganglia of the base of the brain and cortex of HD patients, as well as elevated malondialdehyde (MDA) levels in the blood and 8-hydroxyguanine in the brain [7].…”

The Classification of Microglial Activation Phenotypes on Neurodegeneration and Regeneration in Alzheimer’s Disease Brain

“…The Aβ aggregates are toxic to neurons and synapses, and this leads to innate immune activation of microglia and astrocytes and attendant inflammatory processes, although the exact pathophysiology of this step is largely unknown (McGeer and McGeer, 2010). There is subsequent production and build-up of reactive intermediates and oxygen species that lead to oxidative injury (Kish et al, 1992; Gutowicz, 2011). Other changes in kinase and phosphatase activities lead to the formation of NFTs (Iqbal et al, 1998).…”

Differential Response of Human Embryonic Stem and Somatic Cells to Non-Cytotoxic Hydrogen Peroxide Exposure: An Attempt to Model In Vitro the Effects of Oxidative Stress on the Early Embryo

“…H 2 O 2 is a physiological constituent of living cells, involved in signalling mechanisms and continuously produced via diverse cellular pathways. Under physiological conditions it is relatively stable and less reactive compared to other ROS species and it is able to perform a number of rather specific chemical reactions; moreover, it can react with partially reduced transition metals such as Fe 2+ or Cu 2+ , generating the highly reactive OH− that increases the oxidative damage in the cell [11]. This causes an overload of electrons in the mitochondrial matrix by which cellular oxygen is reduced to O 2 •− , which is subsequently dismutated to H 2 O 2 , generating ROS and damaging the mitochondria [12].…”