Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice
| Autor: | Huayan Hou, Frank Fernandez, Kavon Rezai-Zadeh, R. Douglas Shytle, Maren Jensen, Jun Tan, Gary W. Arendash, Melissa Runfeldt |
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| Rok vydání: | 2007 |
| Předmět: |
Cingulate cortex
medicine.medical_specialty Pathology Amyloid Tau protein Hippocampus Enzyme-Linked Immunosorbent Assay Mice Transgenic tau Proteins Catechin Amyloid beta-Protein Precursor Mice Oral administration Alzheimer Disease Internal medicine medicine Amyloid precursor protein Animals Phosphorylation Maze Learning Molecular Biology Analysis of Variance Amyloid beta-Peptides biology Chemistry General Neuroscience Entorhinal cortex medicine.disease Disease Models Animal Endocrinology Neuroprotective Agents Mutation biology.protein Neurology (clinical) Alzheimer's disease Cognition Disorders Developmental Biology |
| Zdroj: | Brain research. 1214 |
| ISSN: | 0006-8993 |
| Popis: | We previously reported that intraperitoneal (i.p.) injection (20 mg/kg) of (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, decreased beta-amyloid (Abeta) levels and plaques via promotion of the non-amyloidogenic alpha-secretase proteolytic pathway in "Swedish" mutant amyloid precursor protein overexpressing (APPsw, Tg) mice. Here, we find that EGCG administered orally in drinking water (50 mg/kg) similarly reduces Abeta deposition in these mice. Following a six month treatment of an 8 month old cohort, immunohistochemical analysis of coronal sections reveals that plaque burdens were reduced in the cingulate cortex, hippocampus, and entorhinal cortex by 54%, 43%, and 51%, respectively. Congo red plaque burdens were decreased in the cingulate cortex, hippocampus, and entorhinal cortex by 53%, 53%, and 58%, respectively as well. ELISA of brain homogenates of the treatment Tg mice revealed consistent reductions in both Abeta1-40 and 1-42 soluble and insoluble forms. In the present study we also investigated the effect EGCG administration had on tau pathology and cognition in Tg mice. Both i.p. and orally-treated Tg animals were found to have modulated tau profiles, with markedly suppressed sarkosyl-soluble phosphorylated tau isoforms. Radial arm water maze (RAWM) testing for working memory indicated that EGCG provided cognitive benefit to Tg mice with both i.p. and oral administration, although i.p.-treated animals showed a more pronounced benefit because of the greater impairment of their Tg controls at the time of testing. Taken together, these data further the notion of EGCG dietary supplementation as a potentially safe and effective prophylaxis for Alzheimer's disease. |
| Databáze: | OpenAIRE |
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