The relationship between Bcl-2 gene expression and learning & memory impairment in chronic aluminum-exposed rats

Abstract

Aluminum (Al), a known neurotoxin, has been implicated in Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Parkinsonism Dementia Complex, etc., and it causes extensive damage to the nervous system, including the impairment of learning and memory. However, to date, the mechanism of Al neurotoxicity has not been fully elucidated. Neuronal apoptosis has become a focus of interest, as it has been reported to play a key role in the impairment of learning and memory processes (Thompson, Science 267:1456, 1995). The Bcl-2 gene acts as an important effector for inhibiting apoptosis. In the present study we observe neuronal apoptosis in association with learning and memory impairment, as well as regional brain alterations in Bcl-2 expression in rats chronically exposed to Al. The chronic Al-intoxicated model was established by i.p. injection of AlCl3 in adult Sprague Dawley rats for 3 successive days, with one-day intervals, for 60 days. After exposure, the step-down test was performed to examine the behavioral reaction of the rats. Neuronal apoptosis and Bcl-2 protein expression in different regions of rat brain were then assessed by an immunohistochemical method. In the step-down test, the latency of Al-exposed rats was significantly lower than that of controls. Also, the number of performance errors in 5 minutes of exposure was significantly higher than that of controls. Neuronal apoptosis was extensive in the brain of Al-exposed groups, and the expressions of Bcl-2 protein in frontal cortex, cerebellum and hippocampus of Al-exposed rats was stronger. In conclusion, chronic Al-exposure in rats is associated with neuronal apoptosis in brain, and impaired learning and memory. Augmented Bcl-2 protein expression may be a stimulated compensatory mechanism.

Susceptibility of mitochondrial superoxide dismutase to aluminium induced oxidative damage

“…The almost ubiquitous presence of this element has so heavily contaminated the environment that exposure to it is virtually inescapable. A variety of human and animal studies have implicated learning and memory deficits following aluminium exposure (Kaur et al, 2006;Niu et al, 2007), which can be explained on the basis of this being a cholinotoxic agent. Besides, aluminium also has a strong prooxidant activity inspite of its non-redox status (Exley, 2004).…”

Alterations in Trace Elements and Oxidative Stress in Uremic Patients with Dementia

“…Magnesium (Mg) deprivation decreased release of neuronal glutathione (GSH) and caused oxidative death [13]. On the other hand, nonessential element aluminum (Al), a known neurotoxin, can alter the neuronal homeostasis of some essential elements in Alzheimer's disease [14] and cause extensive damage to the nervous system [15]. Among dialysis patients, insufficient dose of dialysis, Al exposure, and malnutrition have also been implicated as risk factors for dementia [16,17]; yet, these findings have not been confirmed.…”

Effects of Aluminium Chloride Exposure on the Histology of the Cerebral Cortex of Adult Wistar Rats

“…Particulate matters distributed by cement -producing factories contain, high amount of Al, and animals and populations residing in the vicinity are exposed to the pollution (Shehla et al, 2001). Although, aluminum has been implicated in Alzheimer's disease, Parkinsonism, Dementia complex and causes extensive damage to the nervous system, to date the mechanism of Al neurotoxicity has not been fully elucidated (Niu et al, 2007). Patients on dialysis or on long-term treatment with total parenteral nutrition have been shown to accumulate this metal in different organs.…”