Alzheimer Diseases
There exists evidence suggesting that memory impairment in AD begins with changes in hippocampal synaptic functions and then gradually progresses to neurodegeneration and neuronal loss in patients of AD, and the Aβ-induced damage in hippocampus might underlie some of the AD behavioral deficits.
Abstract
Copyright © 2014, Hamadan University of Medical Sciences, Hamadan University of Medical Sciences; Published by Hamadan University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Alzheimer's disease (AD), the most common cause of dementia is accompanied by progressive memory loss and other cognitive functions. The conditionis estimated to affect approximately 36 million people, worldwide (1). AD is characterized by the presence of extracellular amyloid β (Aβ) deposits, intracellular neurofibrillary tanglesand senile plaques in the cortex, hippocampus, basal forebrain and amygdale (2). Neurofibrillary tangles formation is the result of intracellular fibrillar aggregation of the microtubule-associated protein tau that is hyperphosphorylated and oxidized. Senile plaques consist of insoluble fibrillar Aβ. It is established that Aβ is formed after sequential cleavage of amyloid precursor protein and secreted to the extracellular space. It also inhibits hippocampal long-term potentiation and disrupts the synaptic plasticity (3). In addition, Aβ accumulation induces an elevation in levels of reactive oxygen species (ROS) in neurons, leading to apoptotic neuronal death in rats and mice (4). Studies showed that the accumulation of Aβ in brain plays an important role in the pathophysiology of AD and a close correlation exits between Aβ procedure and the neurodegeneration process of AD (5). There exists evidence suggesting that memory impairment in AD begins with changes in hippocampal synaptic functions and then gradually progresses to neurodegeneration and neuronal loss in these patients (6). The Aβ-induced damage in hippocampus might underlie some of the AD behavioral deficits. Long-term potentiation (LTP) is one of the most important forms of synaptic plasticity, linked to learning and memory (7). The Aβ makes changes in LTP, in the hippocampus and consequently impairs cognition and memory in rodents (3) and is widely reported to cause lipid peroxidation in brain cell membranes, leading to 4-hydroxy-2-nonenal (HNE) and acrolein formation, both toxic to neurons. These products alter the membrane protein conformation and eventually lead to neuronal death (8). The Aβ initiates free radical processes, resulting in protein oxidation, lipid peroxidation, ROS formation and cellular dysfunction, leading to calcium ion accumulation and subsequent neuronal death (9). Pervious experimental studies have shown that Aβ (25-35) induce a wide pattern of central modifications, reminiscent of the human physiopathology, particularly shortand long-term memory deficit, oxidative stress, apoptosis, neuroinflammation, acetylcholine impairment, hippocampus alteration, tau hyperphosphorylation and amyloid burden (10). The deposition of β-amyloid protein in brain is related to learning impairment and cholinergic neuronal degeneration and the β-amyloid protein-treated rats could be used as AD animal models (11). The key brain regions, involved in the Morris water maze (MWM) task navigation, include the striatum, the frontal lobe and especially, the hippocampus (12). The hippocampus structure has a key role in cognition and psychological function. Animal studies have shown that this structure is rapidly and extremely affected by an Aβ fragment injection (Aβ (25-35)) in rats, damaging the structure and function of the hippocampus (13, 14). The hippocampus plays an important role in contextual memory; the hippocampus injuries negatively affect the MVM task performance (15). Nitta et al. showed that the water maze task performance was impaired in β-amyloid-treated rats, and the choline acetyl transferase activity significantly decreased in the frontal cortex and hippocampus (16). Therefore, the β-amyloid protein deposition in brain is believed to be related to learning impairment and cholinergic neuronal degeneration. It also means that β-amyloid proteintreated rats could be used as animal models for AD (11). Moreover, the studies indicated that intracerebroventricular ( ICV) injection of Aβ (25-35), induced impairment in the passive-avoidance and redial-arm maze tasks, in the rat (11). Maurice confirmed the negative effect of ICV injection of Aβ (25-35) on learning in the Y-maze, passive avoidance and water maze tasks (17). The studies also reported Ar ch ive of S ID