In Vivo and In Vitro Molecular Imaging Techniques to Clarify the Mechanism of Oxidative Stress Related to Brain Aging and Neuro-degenerative Diseases

Toru      Sasaki

doi:10.2174/1568015043477621

Abstract

Reactive oxygen species (ROS) are considered to be the cause of oxidative stress, and consequently, ROS significantly contribute to aging and various diseases. Oxidative stress involves an imbalance (oxidants vs antioxidants) inclining toward oxidation, and is significant especially in the brain, because much oxygen is consumed and concentrations of antioxidants and related enzymes are relatively low. Therefore, it is considered that oxidative stress is closely related to the mechanisms of brain aging and neurodegenerative diseases. This paper reviews in vivo and in vitro molecular imaging techniques, with the results of imaging used to assess the molecular mechanism of oxidative stress, originating from the mitochondria of cerebral tissue. The mitochondrial electron transfer function, which can be inhibited by in vitro simulated ischemia, causes glycolysis to switch from an aerobic (36 ATP molecules formed from one glucose molecule) to anaerobic process (2 ATP molecules formed from one glucose molecule). Under anaerobic conditions, glucose uptake into cells is enhanced because of the low efficiency of ATP formation. This causes the stimulation of ROS formation when aerobic conditions return. The content of glutathione (GSH), a major antioxidant in the brain, and mitochondrial electron transport function decrease with age, whereas glucose transport and metabolism are maintained throughout the aging process. It is thought that glucose metabolism remains constant with increasing age to compensate for the decreased efficiency of electron transfer in the mitochondria; a phenomenon that is also observed in cerebral ischemia. Mitochondria are one of the main sources of ROS, because 95% of molecular oxygen is metabolized within mitochondria, and 2% of metabolized oxygen is converted to ROS as a byproduct, even under normal conditions. The mitochondrial GSH concentration is maintained at a high level by the transport system located on the inner membrane of the mitochondria. Manganese-superoxide dismutase (Mn-SOD) decomposes . O2 - in mitochondria. However, ROS may form at a rate that exceeds the mitochondrial antioxidants and antioxidative enzymes. This causes an accumulation of oxidative damage at the molecular level. Such damage leads to delayed neuronal death through the release of apoptogenic factors such as cytochrome c, from the mitochondrial membrane. To limit oxidative stress in mitochondria, the development of antioxidant related drugs and effective methods of delivering these drugs into mitochondria are required to prevent and / or cure brain aging and neurodegenerative diseases.

Keywords: metabolized, mitochondrial, oxygen, GSH concentration, glucose, antioxidant, Manganese-superoxide

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