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      Vitamin E therapy prevents the accumulation of congophilic amyloid plaques and neurofibrillary tangles in the hippocampus in a rat model of Alzheimer’s disease

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          Abstract

          Objective(s):

          Vitamin E may have beneficial effects on oxidative stress and Aβ-associated reactive oxygen species production in Alzheimer’s disease. But, the exact role of vitamin E as a treatment for Alzheimer’s disease pathogenesis still needs to be studied. Hence, we examined the therapeutic effects of vitamin E on

          the density of congophilic amyloid plaques and neurofibrillary tangles in rats’ hippocampi.

          Materials and Methods:

          Wistar rats were randomly assigned to control (no drug treatment), sham scopolamine (3 mg/kg)+saline and Sham scopolamine+sesame oil groups, and three experimental groups that received scopolamine+vitamin E (25, 50, and 100 mg/kg/day) daily for 14 days after scopolamine injection. The rats’ brains were collected immediately following transcardial perfusion and fixed in 4% paraformaldehyde. Pathological brain alterations were monitored through Congo red and bielschowsky silver staining.

          Results:

          Scopolamine treatment led to a significant increase in the density of congophilic amyloid plaques and neurofibrillary tangles in the hippocampus. IP injection of vitamin E in three doses (25, 50, and 100 mg/kg/day) significantly reversed the scopolamine-induced increase of the congophilic amyloid plaque density and density of neurofibrillary tangles in the hippocampus. Although vitamin E (25 and 50 mg/kg/day) doses were also effective, but a 100 mg/kg/day dose of vitamin E was more effective in the reduction of congophilic amyloid plaque and neurofibrillary tangle density.

          Conclusion:

          Vitamin E could exert a therapeutic effect in the reduction of congophilic amyloid plaque and neurofibrillary tangle density in the hippocampus of scopolamine-treated rats and it is useful for Alzheimer’s disease.

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          Most cited references42

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          Vitamin E and donepezil for the treatment of mild cognitive impairment.

          Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo. Copyright 2005 Massachusetts Medical Society.
            • Record: found
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            • Article: not found

            Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases.

            The salutary intersection of fundamental cell biology with the study of disease is well illustrated by the emerging elucidation of neurodegenerative disorders. Novel mechanisms in cell biology have been uncovered through disease-orientated research; for example, the discovery of presenilin as an intramembrane aspartyl protease that processes many diverse proteins within the lipid bilayer. A common theme has arisen in this field: normally-soluble proteins accumulate, misfold and oligomerize, inducing cytotoxic effects that are particularly devastating in the post-mitotic milieu of the neuron.
              • Record: found
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              • Article: not found

              The validity of scopolamine as a pharmacological model for cognitive impairment: a review of animal behavioral studies.

              Scopolamine is used as a standard/reference drug for inducing cognitive deficits in healthy humans and animals. Effects are often interpreted in terms of a role of acetylcholine in mnemonic and/or attentional processes. In this paper an overview is given of the effects of scopolamine on animal behavior. Examination of the dose-response curve of systemically administered scopolamine indicates that sensory discrimination and attention are most sensitive to disruption. When higher doses (>0.03mg/kg) are used, deficits in other cognitive and non-cognitive functions (e.g., learning and memory, locomotor activity) are reported. Several behavioral processes (taste aversion, anxiety, short-term memory, attention) are found to be affected after intracerebral injections of scopolamine. It is concluded that effects on learning and memory performance which are observed after higher doses of scopolamine are mediated by (1) primary effects on attention and sensory/stimulus discrimination, (2) non-specific effects on behavior (e.g., locomotor activity, anxiety), and (3) peripheral side-effects (e.g., pupil dilation, salivation). Finally, the validity of scopolamine as a pharmacological model for cognitive impairment is discussed. The use of muscarinic M1 antagonists is suggested as a more selective and effective way of inducing cholinergic-induced cognitive deficits.

                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                ijbms
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                January 2020
                : 23
                : 1
                : 86-92
                Affiliations
                [1 ]Neuroscience Research Center, Department of Anatomy, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
                [2 ]Neuroscience Research Center, Golestan University of Medical Sciences, Gorgan, Iran
                Author notes
                [* ]Corresponding author: Mehrdad Jahanshahi. Neuroscience Research Center, Department of Anatomy, Faculty of Medicine, Gorgan University of Medical Sciences, km 4 Gorgan-Sari road (Shastcola), Gorgan, Iran.Tel/Fax: +98-17-32453515; Email: mejahanshahi@yahoo.com
                Article
                10.22038/IJBMS.2019.38165.9067
                7206846
                32395206
                1c4331f6-00da-4c15-aafd-6a69c0096a14

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 February 2019
                : 21 July 2019
                Categories
                Original Article

                amyloid plaque,hippocampus,neurofibrillary tangles,rat,vitamin e

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