A glutamatergic mechanism for aluminum toxicity in astrocytes

Zielke, H. Ronald; Jackson, M J; Tildón, J. Tyson; Max, Stephen R.

doi:10.1007/bf03160001

Cited by 20 publications

(10 citation statements)

References 49 publications

(31 reference statements)

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“…GSH acts as a cellular reductor whose main function is to protect against oxidative stress and cellular aging. In accordance with Bondy et al [32], an increase has been also observed in brain tissues, a result similar to the results reported in astroglia culture by Zielke et al [33].…”

Section: Discussionsupporting

confidence: 92%

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Aluminum‐induced pro‐oxidant effects in rats: protective role of exogenous melatonin

Esparza

Gómez

Romeu

et al. 2003

Journal of Pineal Research

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In recent years, it has been suggested that oxidative stress is a feature of Alzheimer's disease in which aluminum (Al) could exacerbate oxidative events. The goal of the present study was to assess in rats the pro-oxidant effects induced by Al exposure, as well as the protective role of exogenous melatonin. Two groups of male rats were intraperitoneally injected with Al only or melatonin only, at doses of 5 and 10 mg/kg/day, respectively for 8 wk. During this period, a third group of animals received Al (5 mg/kg/day) and melatonin (10 mg/kg/day). At the end of the treatment period, rats were anesthesized and arterial blood was obtained. Thereafter, animals were killed and liver and brain (cortex, hippocampus and cerebellum) were removed. These tissues were processed to examine oxidative stress markers: glutathione transferase (GST), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), thiobarbituric acid reactive substances (TBARS), as well as protein content. Samples of these tissues were also used to determine Al, Fe, Mn, Cu and Zn concentrations. The results show that Al exposure promotes oxidative stress in different neural areas, including those in which Al concentrations were not significantly increased. The biochemical changes observed in neural tissues show that Al acts as pro-oxidant, while melatonin exerts an antioxidant action in Al-treated animals. The protective effects of melatonin against cellular damage caused by Al-induced oxidative stress, together with its low toxicity, make melatonin worthy of investigation as a potential supplement to be included in the treatment of neurological disorders in which the oxidative effects must be minimized.

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Section: Discussionsupporting

confidence: 92%

“…[32], an increase has been also observed in brain tissues, a result similar to the results reported in astroglia culture by Zielke et al. [33].…”

Section: Discussionsupporting

confidence: 85%

Aluminum‐induced pro‐oxidant effects in rats: protective role of exogenous melatonin

Esparza

Gómez

Romeu

et al. 2003

Journal of Pineal Research

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“…Direct toxicity refers to the physical presence (or close proximity) of aluminum and its potential for initiating cell death pathways. Accumulation of aluminum into the cytoplasm via cellular uptake mechanisms or diffusion could cause alterations in glutaminase and glutamine synthetase and easily alter the availability of the neurotransmitter glutamate [47]. Aluminum acting to induce abnormal tau protein accumulation could also increase neurofibrillary tangles and impair cellular transport mechanisms [48].…”

Section: Discussionmentioning

confidence: 99%

Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration

Shaw

Petrik

2009

Journal of Inorganic Biochemistry

163

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Gulf War Syndrome is a multi-system disorder afflicting many veterans of Western armies in the 1990-1991 Gulf War. A number of those afflicted may show neurological deficits including various cognitive dysfunctions and motor neuron disease, the latter expression virtually indistinguishable from classical amyotrophic lateral sclerosis (ALS) except for the age of onset. This ALS "cluster" represents the second such ALS cluster described in the literature to date. Possible causes of GWS include several of the adjuvants in the anthrax vaccine and others. The most likely culprit appears to be aluminum hydroxide. In an initial series of experiments, we examined the potential toxicity of aluminum hydroxide in male, outbred CD-1 mice injected subcutaneously in two equivalent-tohuman doses. After sacrifice, spinal cord and motor cortex samples were examined by immunohistochemistry. Aluminum-treated mice showed significantly increased apoptosis of motor neurons and increases in reactive astrocytes and microglial proliferation within the spinal cord and cortex. Morin stain detected the presence of aluminum in the cytoplasm of motor neurons with some neurons also testing positive for the presence of hyper-phosphorylated tau protein, a pathological hallmark of various neurological diseases, including Alzheimer's disease and frontotemporal dementia. A second series of experiments was conducted on mice injected with six doses of aluminum hydroxide. Behavioural analyses in these mice revealed significant impairments in a number of motor functions as well as diminished spatial memory capacity. The demonstrated neurotoxicity of aluminum hydroxide and its relative ubiquity as an adjuvant suggest that greater scrutiny by the scientific community is warranted.

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“…The increase in GFAP was most likely the response to aluminum -induced neuronal damage since research has shown that astrocytes exposed directly to aluminum do not increase production of GFAP (Toimela and Tahti 1995). Exposed glia do accumulate aluminum and show cellular changes indicative of both glutamatergic (Zielke et al 1993) and oxidative stress (Campbell et al 1999). Though neurons are known to be more vulnerable than glial cells in conditions in which oxidative stress is thought to play primary or secondary roles, such as ischemia, hypoxia, and brain trauma.…”

Section: Control (N-c) Aluminium (N-a) Control (G-c) Aluminium (G-a)mentioning

confidence: 96%

Antioxidant Enzymatic System in Neuronal and Glial Cells Enriched Fractions of Rat Brain After Aluminum Exposure

Khanna

Nehru

2007

Cell Mol Neurobiol

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The aim of this work was to investigate as to how neurons and glial cells separated from the brain cortex respond to oxidative stress induced by aluminum. Female SD rats were exposed to aluminum at the dose level of 100 mg/kg b.w. for 8 weeks. Neuronal and glial cell-enriched fractions were obtained from rat cerebral cortex by sieving the trypsinated homogenate through a series of nylon meshes, followed by centrifugation on ficoll density gradient. Total glutathione content, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-s-transferase (GST) along with antioxidant enzymes superoxide dismutase (SOD), catalase were estimated in neuronal and glial-enriched fractions in both control (N-c and G-c) and aluminum exposed animals (N-a and G-a). Secondary products of lipid peroxidation that is MDA levels were estimated by measuring the (TBARS) levels. Our results indicate that TBARS levels were significantly higher in glial cell fraction of unexposed controls (Gc) than the neuronal cells (Nc). Correspondingly the glial cells had higher levels of GSH, GSSG, GPx and GST where as neurons had higher levels of catalase, SOD and GR. Following aluminum exposures significant increase in the TBARS levels was observed in neurons as compared to glial cells which also showed a significant decrease in SOD and catalase activity. The decrease in the TBARS levels in the glial cells could be related to the increase in the GSH levels, GR activity, and GST activity which were found to be increased in glial enriched fractions following aluminum exposure. The increase in activity of various enzymes viz GR, GST in glial cells as compared to neurons suggests that glial cells are actively involved in glutathione homeostasis. Our conclusion is that glial and neurons isolated from rat cerebral cortex show a varied pattern of important antioxidant enzymes and glial cells are more capable of handling the oxidative stress conditions.

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A glutamatergic mechanism for aluminum toxicity in astrocytes

Cited by 20 publications

References 49 publications

Aluminum‐induced pro‐oxidant effects in rats: protective role of exogenous melatonin

Aluminum‐induced pro‐oxidant effects in rats: protective role of exogenous melatonin

Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration

Antioxidant Enzymatic System in Neuronal and Glial Cells Enriched Fractions of Rat Brain After Aluminum Exposure

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