A behavioral and ultrastructural dissection of the interference of aluminum with aging (original) (raw)
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Journal of Alzheimer's disease : JAD, 2003
The effect of chronic aluminum intake has been investigated in the brain of aged male Wistar rats to assess the potential role of the accumulation of this metal ion on the development of neurodegenerative features observed in Alzheimer's disease. AlCl3 x 6 H2O (2g/L) was administered to experimental animals for 6 months in the drinking water. The total content of Al (microg/g fresh tissue) was measured by inductively coupled plasma atomic emission spectrometry (ICP-AES), while the content of Cu, Zn and Mn was determined by flame AAS in the prosencephalon + mesencephalon, pons-medulla and cerebellum of control and Al(III)-treated animals. The area occupied by mossy fibres in the CA3 field of the hippocampus was estimated by a computer-assisted morphometric method following Timm's preferential staining. In Al(III)-treated rats the concentration of Cu, Zn and Mn did not increase significantly (p < 0.5) in prosencephalon + mesencephalon, nor in pons-medulla (p < 0.5) excep...
A BEHAVIORAL AND HISTOLOGICAL STUDY OF THE EFFECTS OF LONG-TERM EXPOSURE OF ADULT RATS TO ALUMINUM
International Journal of Neuroscience, 2003
. The effects of Al long-term exposure were investigated to describe the associated behavioral and brain modifications. Adult rats were intraperitoneally injected three times a week for 6 months with ecological doses of Al gluconate (0.85 mg/kg). The Al overload was confirmed by the significantly increased level of Al in serum. We assessed fear conditioning, spatial memory and emotional reactivity by shuttle-box task, Morris water maze, and open-field, respectively. The performance of the experimental animals at the shuttle-box task was significantly lower (p < .01) compared to that of control. The experimental animals had impaired spatial memory, with lower and more fluctuant performance at Morris water maze. The noxious-driven behavior of the experimental animals was also altered, with significantly lower activity scores (p < .05), and high emotionality scores (p < .01) at the open-field. We recovered and processed the brain for aluminum and amyloid deposits. The brains of experimental animals, studied by optical microscopy, displayed a massive cellular depletion in the hippocampal formation, particularly, the CAl field, and also in the temporal and parietal cortex. We observed numerous ghost-like neurons with cytoplasmic and nuclear vacuolations, and with Al deposits. The hippocampus contained extracellular accumulations of Al and amyloid surrounded by nuclei of degenerating cells, which we interpreted as neuritic plaques. The cerebrovasculature was distorted, with a significant thickening of the wall of capillaries, associated with amyloid deposits. These behavioral and neuropathological modifications associated with long-term exposure to Al are reminiscent of those observed in AD.
Aluminum and Alzheimer's disease: a new look
Journal of Alzheimer's disease : JAD, 2006
Despite the circumstantial and sometimes equivocal support, the hypothetic involvement of aluminum (Al) in the etiology and pathogenesis of Alzheimer's disease (AD) has subsisted in neuroscience. There are very few other examples of scientific hypotheses on the pathogenesis of a disease that have been revisited so many times, once a new method that would allow a test of Al's accumulations in the brain of AD patients or a comparison between Al-induced and AD neuropathological signs has become available. Although objects of methodological controversies for scientists and oversimplification for lay spectators, several lines of evidence have strongly supported the involvement of Al as a secondary aggravating factor or risk factor in the pathogenesis of AD. We review evidence on the similarities and dissimilarities between Al-induced neurofibrillary degeneration and paired helical filaments from AD, the accumulation of Al in neurofibrillary tangles and senile plaques from AD, the...
Aluminium exposure induces Alzheimer's disease-like histopathological alterations in mouse brain
Histology and histopathology, 2008
Aluminium (Al) is a neurotoxic metal and Al exposure may be a factor in the aetiology of various neurodegenerative diseases such as Alzheimer's disease (AD). The major pathohistological findings in the AD brain are the presence of neuritic plaques containing beta-amyloid (Abeta) which may interfere with neuronal communication. Moreover, it has been observed that GRP78, a stress-response protein induced by conditions that adversely affect endoplasmic reticulum (ER) function, is reduced in the brain of AD patients. In this study, we investigated the correlation between the expression of Abeta and GRP78 in the brain cortex of mice chronically treated with aluminium sulphate. Chronic exposure over 12 months to aluminium sulphate in drinking water resulted in deposition of Abeta similar to that seen in congophilic amyloid angiopathy (CAA) in humans and a reduction in neuronal expression of GRP78 similar to what has previously been observed in Alzheimer's disease. So, we hypothesi...
Brain Research, 2009
Aluminum exposure is known to be associated with oxidative stress and cognitive decline in experimental animals but the precise mechanism of its neurotoxicity has not yet been delineated. The present study attempts to assess the learning and memory capacity of rats using Y-maze test for cognitive functioning. The markers of oxidative stress, e.g. lipid peroxides and endogenous antioxidants as well as metals (Al, Fe, Cu, Zn and Se) were measured in the brain frontal cortex of young and aged rats fed with AlCl3 (100 mg/kg b.w.) for 90 days and normal saline treated controls. We observed significant changes between young and aged Al treated rats and their controls in terms of lipid peroxides and endogenous antioxidants. Lipofuscin content was significantly increased in Al treated aged rats along with higher concentration of Al, Fe and Zn with concomitantly low levels of Cu, and Se. Ultrastructural studies of the frontal cortex of exposed rats revealed that the changes were more pronounced in the aged treated rats in terms of presence of spongiform lipofuscin, vacuolization and lysosomal degradation. Changes in synaptic morphology and decreased number of synapses were detected in the frontal cortex of Al treated aged rats. On the basis of the results of the present study, we conclude that Al may be linked with neurolipofuscinogenesis and alteration in neurobehavioral activity and these changes may be responsible for the development of age related disorders, such as Alzheimer’s disease.
Aluminium in Alzheimer’s disease: are we still at a crossroad
Experientia, 2005
Aluminium, an environmentally abundant non-redox trivalent cation has long been implicated in the pathogenesis of Alzheimer’s disease (AD). However, the definite mechanism of aluminium toxicity in AD is not known. Evidence suggests that trace metal homeostasis plays a crucial role in the normal functioning of the brain, and any disturbance in it can exacerbate events associated with AD. The present paper reviews the scientific literature linking aluminium with AD. The focus is on aluminium levels in brain, region-specific and subcellular distribution, its relation to neurofibrillary tangles, amyloid beta, and other metals. A detailed mechanism of the role of aluminium in oxidative stress and cell death is highlighted. The importance of complex speciation chemistry of aluminium in relation to biology has been emphasized. The debatable role of aluminium in AD and the cross-talk between aluminium and genetic susceptibility are also discussed. Finally, it is concluded based on extensive literature that the neurotoxic effects of aluminium are beyond any doubt, and aluminium as a factor in AD cannot be discarded. However, whether aluminium is a sole factor in AD and whether it is a factor in all AD cases still needs to be understood.
Molecular toxicity of aluminium in relation to neurodegeneration
The Indian journal of medical research, 2008
Exposure to high levels of aluminium (Al) leads to neurofibrillary degeneration and that Al concentration is increased in degenerating neurons in Alzheimer's disease (AD). Nevertheless, the role of Al in AD remains controversial and there is little proof directly interlinking Al to AD. The major problem in understanding Al toxicity is the complex Al speciation chemistry in biological systems. A new dimension is provided to show that Al-maltolate treated aged rabbits can be used as a suitable animal model for understanding the pathology in AD. The intracisternal injection of Al-maltolate into aged New Zealand white rabbits results in pathology that mimics several of the neuropathological, biochemical and behavioural changes as observed in AD. The neurodegenerative effects include the formation of intraneuronal neurofilamentous aggregates that are tau positive, oxidative stress and apoptosis. The present review discusses the role of Al and use of Al-treated aged rabbit as a suitab...
Toxicology, 2014
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