Role of oxidative stress in animal model of Alzheimer?s disease

O damage, mitochondrial dysfunction and inflammation underlies many common aging-related neurodegenerative diseases, including AD. The major pathological hallmark of AD is the accumulation of Aβ peptides in the brain. Nitric oxide (NO) is a signaling molecule produced by neurons and endothelial cells in the brain. A high level of NO is implicated in pathological process of neurological and aging-related disorders. A single Aβ administration into the rat hippocampus could induce increase of NOS activity and NO level. NO-derived peroxynitrite could cause irreversible injury to the mitochondria, inhibiting all complexes. This leads to reduced ATP formation and induction of opening of the permeability transition pore, release of cytochrome c and activation of caspase. It has been shown that Aβ peptide triggers the activation of caspase-3, which eventually results in neuronal apoptosis. Oxidative insults that induce neuronal apoptosis, including agents that induce membrane lipid peroxidation, have been shown to activate caspases (particularly caspase-3). Increased lipid peroxidation was consistently observed in an animal model of Alzheimer amyloidosis. In the Aβ (1–42)-treated hippocampus, MDA and carbonyl protein levels were significantly higher and GSH was markedly lower, further demonstrating that Aβ induced oxidative stress, and that the antioxidant defenses were unable to offset the oxidant. On the other hand, the low levels of GSH directly denoted the increased ROS/RNS, lipid peroxides, and highly reactive hydroxyl radicals. Despite this role, the induction of GSH synthesis seems not to be enough to protect the cells from the NO effect; the increase in GSH level occurs when caspase-3 is already activated and thus the apoptotic process is already in progress.