Role of Oxidative Stress in Aβ Animal Model of Alzheimer's Disease: Vicious Circle of Apoptosis, Nitric Oxide and Age

The aging process is believed to be closely related to increased oxidative stress. Reactive intermediates of oxidative stress affect the cellular redox status and induce apoptosis [1]. Oxidative stress due to the loss of balance between ROS production and antioxidant defenses affects all the vital organs, resulting in aging [1,2]. Oxidative damage, mitochondrial dysfunc‐ tion and inflammation underlies many common aging-related neurodegenerative diseases, including AD [2,3]. The major pathological hallmark of AD is the accumulation of Aβ peptides in the brain [4]. Oxidative insults that induce neuronal apoptosis, including agents that induce membrane lipid peroxidation, also have been shown to activate caspases [5]. Increased lipid peroxidation was consistently observed in some animal models of Alzheimer amyloidosis [4, 6]. It has been shown that a single Aβ administration into the rat hippocampus could induce increase of NOS activity and NO level [6]. Nitric oxide is a multifunctional molecule that acts as messenger/modulator in synaptogenesis and potential neurotoxin and is synthesized by three isozymes of Nitric oxide synthase (NOS) [7]. Oxidative stress reflects a situation in which ROS is continuously produced and exceeds the capacity of endogenous antioxidant defense systems. Several studies have suggested that oxidative stress plays a key role in Aβ-mediated neuronal cytotoxicity by triggering or facilitating neurodegeneration through a wide range of molecular events that eventually lead to neuronal cell loss. Aβ significantly increases produc‐ tion and enhances membrane lipid peroxidation, leading to neuronal apoptosis [8,9]. Because multiple factors are involved in the pathogenesis of the AD, it is difficult to find an ideal in vivo model. It is important to determine Aβ 1-42 injection effects especially in hippocampus,