Oxidative Stress and the Central Nervous System

Abstract

Biochemical integrity of the brain is vital for normal functioning of the central nervous system (CNS). One of the factors contributing to cerebral biochemical impairment is a chemical process called oxidative stress. Oxidative stress occurs upon excessive free radical production resulting from an insufficiency of the counteracting antioxidant response system. The brain, with its high oxygen consumption and lipid-rich content, is highly susceptible to oxidative stress. Therefore, oxidative stress-induced damage to the brain has a strong potential to negatively impact normal CNS functions. Although oxidative stress has historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer disease, Huntington disease, and Parkinson disease, its involvement in neuropsychiatric disorders, including anxiety disorders and depression, is beginning to be recognized. This review is a discussion of the relevance of cerebral oxidative stress to impairment of emotional and mental well-being.

Fig. 1.

Schematic representation of how oxidative stress might lead to cognitive and behavioral deficits. Persistent psychologic stress disrupts oxidant-antioxidant balance within the brain, causing reduction in antioxidant enzyme function of glyoxalase (GLO)-1, glutathione reductase (GSR)-1, manganese superoxide dismutase (Mn SOD), and Cu/Zn SOD. This leads to glutathione depletion, causing oxidative stress. Simultaneously occurring glutamate toxicity, calcium imbalance, and mitochondrial impairment collectively intensify oxidative stress, causing biochemical distress in the brain. This disrupts neurocircuitry, weakening hippocampal, amygdalar, and cortical connections and ultimately causing behavioral and cognitive deficits.