Behavioral effects of aluminum ingestion on animal and human subjects (original) (raw)
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Aluminum toxicity to the brain
Science of The Total Environment, 1988
BACKGROUND The connection to metal toxicity in the brain is proven by aluminum's presence in the neurons (brain cells) of autopsied patients who had suffered from Alzheimer's disease. Aluminum is the most commonly found toxic metal that permeates such affected brains. In 1897, aluminum was analyzed for pathological reaction in animals and reported to be a selective neurotoxin. Thereafter it was recognized as a human poison that caused loss of memory, jerking movements, and impaired coordination. In 1980, Drs. D.P. Perl, and P.F. Good, two neuropathologists at Mt. Sinai Medical Center in New York City, discovered that not only did aluminum show up generally in the brains of Alzheimer's disease victims, but it was also present in precisely those tangled brain cells that characterized the disease. Daniel Perl, M.D., found a baffling wave of degenerative brain disease in the Pacific Island of Guam. About 10 percent die of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease) and parkinsonism with dementia (PD). There are high levels of aluminum in the drinking water and in nineteen common foods of Guam and Rota. Dr. Perl repeatedly has found the metal in the brains of deceased Mariana islanders who had been afflicted with ALS and PD.
Studies of aluminum in rat brain
Biological trace element research, 1987
The effects of high aluminum concentrations in rat brain were studied using(14)C autoradiography to measure the uptake of [(14)C]2deoxy-D-glucose ([(14)C]2DG) and microbeam proteon-induced X-ray emission (microPIXE) with a 20-μm resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T), and control animals were given sodium tartrate (Na-T). The(14)C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes, which included cerebral cortical atrophy. The results showed that there was a decreased uptake of [(14)C]2DG in cortical regions in which increased aluminum levels were measured, i.e., there was a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppm (mass fraction) or 3×10(9) Al atoms was obtained for Al under the conditions employed.
Accumulation of aluminum in rat brain
Biological Trace Element Research, 2003
The present study was undertaken to examine possible aluminum (Al) accumulation in the brain of rats and to investigate whether subchronic exposure to the metal leads to behavioral and neurophysiological changes in both treated and control groups. Each of the groups consisted of 10 animals. Aluminum chloride (AlCl3) at a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by gavage for 8 wk. Al-free water by gavage was given to the control group throughout the experiment. Behavioral effects were evaluated by open-field (OF) motor activity and by acoustic startle response (ASR). Electrophysiological examination was done by recording spontaneous activity and sensory-evoked potentials from the visual, somatosensory, as well as auditory cortex. The Al content of each whole brain was determined by electrothermal atomic absorption spectrophotometry. Subchronic Al exposure slightly caused some changes in the evoked potentials and electrocorticograms and in the OF and ASR performance, but these results were not statistically significant. The brain Al levels of the control and the low and high dose of Al-exposed groups were measured as 0.717±0.208 µg/g (wet weight), 0.963±0.491 µg/g (wet weight) and 1.816±1.157 µg/g (wet weight), respectively.
Review of epidemiologic studies of aluminium and neurological disorders
Environmental Geochemistry and Health, 1990
The epidemiological study of neurological disorders is just beginning and should he continued because of the potential public health impact of these diseases on society. The most important contribution of epidemiologicai research is the identification of risk factors, and specific disease entities, such as Alzheimer's disease, should be studied. Ecological analysis of geographical data have associated a small increase in mortality from Alzheimer's disease and dementia with the aluminium content of drinking water. These results must necessarily be interpreted with caution because serious errors may result from inferences based on ecological analysis, e.g. "the ecologic fallacy". Potential risk factors for Alzheimer's disease have been studied in case-comparison epidemiology studies conducted in Italy, Massachusetts, Colorado, Minnesota and North Carolina, but only two studies have considered aluminium exposure, through the use of antacids. Although no increased risk was found to be associated with aluminium exposure, only a small number of individuals in the studies reported antacid use, and the studies had an extremely limited statistical power to detect an association. Additional analytical epidemiology studies, either cohort or case-comparison, are required to better describe the possible relationship between aluminium and Alzheimer's disease. These studies should be designed according to well-established epidemiological principles, be conducted with no selection bias and minimum observation bias, consider potential confounding and modifying factors, and have sufficient statistical power to enable detection of low relative risks.
Journal of Neuroscience and Neurosurgery
The development of psychotropic has slowed over the last two decades for essentially economic reasons; the drug industry has invested more in the field of oncology and autoimmune diseases. However, there are still avenues to explore, such as allostery for the development of drugs in the field of anxiety depression, bipolarity in particular. Other concepts are suggested in this article as the β-arrestins potential therapeutic targets in Alzheimer's disease (AD), the inhibitors of phosphodiesterase 10A for Huntington's disease, and the epigenetic in schizophrenia, peroxisome proliferator-activated receptors in neurodegenerative diseases.
Aluminum in Neurological Disease - a 36 Year Multicenter Study
Journal of Alzheimer’s Disease & Parkinsonism, 2018
Aluminum is a ubiquitous neurotoxin highly enriched in our biosphere, and has been implicated in the etiology and pathology of multiple neurological diseases that involve neural degeneration, behavioral impairment and cognitive decline. Over the last 36 years our group has analyzed the aluminum content of the temporal lobe neocortex of 511 high quality human brain samples from 18 diverse neurological and neurodegenerative disorders, including 2 groups of age-matched controls. Brodmann anatomical areas including the inferior, medial and superior temporal gyrus (A20-A22) were selected for analysis: (i) because of their essential functions in massive neural information processing operations including cognition and memory formation; and (ii) because subareas of these anatomical regions are unique to humans and are amongst the earliest areas affected by progressive neurodegenerative disorders such as Alzheimer's disease (AD). We utilized the analytical technique of (i) Zeeman-type electrothermal atomic absorption spectrophotometry (ETAAS) combined with (ii) an experimental multi-elemental analysis using the advanced photon source (APS) ultra-bright storage ring-generated hard X-ray beam (7 GeV) and fluorescence raster scanning (XRFR) spectroscopy device at the
Aluminum and Neurodegenerative Diseases
Elsevier eBooks, 2017
Aluminum (Al) is a common element found in large amounts in the earth's crust (Priest et al., 1988). Aluminum-containing minerals are present in relatively inert rock types, especially in igneous formations, such as granite and quartz. Laterization of various silicate rocks weathering into finer particles results in the formation of sedimentary bauxite, where together with iron, Al is present largely as the oxide. It is as bauxite that Al is generally mined and second only to iron, Al is the most widely used metal (Hetherington, 2007). Despite its commonality, Al has no known beneficial biological roles and is not an essential element for any organism. Aluminum-containing minerals are rather unreactive, and this is also true for metallic aluminum, as this is quickly oxidized in air and thus coated by a very thin but robust layer of the oxide. This apparent inertness has led to the concept that aluminum may not constitute a health hazard. Consequently a wide range of Al compounds have been added as stabilizers in many processed foods. Alum, which is any trivalent Al-containing salt, is the oldest and most commonly used vaccine adjuvant. Recent findings indicate that the effectiveness of the adjuvant relies on both its immunomodulatory as well as inflammatory properties. Al salts have also found utility in water clarifying processes by effecting precipitation of organic particulate matter. Growing incidence of acidic rain has led to greater solubilization of aluminum salts from their insoluble form in rocks. This has led to an elevated Al content in many water reserves used for residential supply. Thus, human exposure to more soluble forms of Al in water and foodstuffs has grown. Reports from both biological laboratories and from study of human population health indicate that prolonged aluminum ingestion can result in neurological abnormality. Accumulating indications strongly suggest that Al can further the onset and development of neurodegenerative disorders, principally Alzheimer's disease (AD). There are many reports suggesting that Al can provoke excessive inflammatory events in the brain. Superfluous immune reactivity that is not an obvious response to a trauma such as injury or infection is a distinguishing feature of the elderly brain and appears exacerbated in nervous system abnormalities. Most neurodegenerative diseases have no obvious cause and do not have a clear genetic basis. Thus, it is probable that the origin of such diseases lies in unknown environmental influences that interact with the progression of aging. The nature of most of such factors is unknown, but there is growing evidence, indicating that Al is likely to be one of these environmental factors. In this review, reports that point to the conclusion that aluminum are able to speed up the worsening of brain function with age, and potential mechanisms are discussed. It should be noted that acceleration of this process would inevitably increase the prevalence of those specific neurological disorders where age is a concomitant risk factor. 2 Growing Bioavailability of Aluminum in the Environment Metallic aluminum was first made by Hans Oersted in 1825 by heating aluminum chloride with elemental potassium (Sigel and Sigel, 1988). Al-containing chemicals have many uses. Mixing aluminum sulfate and lime together in water leads to formation of colloidal aluminum hydroxide, and this can bring about precipitation and removal of waterborne organic material. This method for water clarification is widely used. Al-containing additives are also found in many foodstuffs. They are used as emulsifying agents in preparation of processed cheese, as crisping agents in pickles, in baking powder, and in a variety of food colorings. Aluminum-containing compounds are also found in cosmetics. Commercial preparations of infant formula can contain significant amounts of the metal (Burrell and Exley, 2010; Dabeka et al., 2011). High concentrations of soluble Al can be found in the juice resulting from boiling of acidic fruit in aluminum cookware (Fimreite et al., 1997). The aluminum content of city water supplies is variable, but on occasion, concentrations as high as 0.4-1 mg/L have been reported in drinking water. Although the health effects of these levels of the metal on humans are uncertain, the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives in 2007 recommended a maximum intake of Al less than 1 mg/kg body weight per week. This corresponds to 63 mg per week for a 140-pound adult. Some commercial pastry products contain Al