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Diet Supplementation with Hydroxytyrosol Ameliorates Brain Pathology and Restores Cognitive Functions in a Mouse Model of Amyloid-β Deposition.
- Source :
-
Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2018; Vol. 63 (3), pp. 1161-1172. - Publication Year :
- 2018
-
Abstract
- Alzheimer's disease is the most common form of dementia affecting a large proportion of aged people. Plant polyphenols have been reported to be potentially useful in the prevention of AD due to their multiple pharmacological activities. The aim of the present study was to assess whether the previously reported neuroprotective and anti-inflammatory effects resulting from oleuropein aglycone administration were reproduced by diet supplementation with similar amounts of its metabolite hydoxytyrosol (HT). Four-month-old TgCRND8 and wild type mice were treated for 8 weeks with a low-fat diet (5%) supplemented with HT (50 mg/kg of diet). We found that HT supplementation significantly improved cognitive functions of TgCRND8 mice and significantly reduced Aβ42 and pE3-Aβ plaque area and number in the cortex; in the hippocampal areas of HT-fed TgCRND8 mice, we found a significant reduction in the pE3-Aβ plaque number together with a tendency toward a reduction in Aβ42 load and pE3-Aβ plaque area, associated with a marked reduction of TNF-α expression and astrocyte reaction. Macroautophagy induction and modulation of MAPKs signaling were found to underlie the beneficial effects of HT. Our findings indicate that HT administration reproduces substantially the beneficial effects on behavioral performance and neuropathology previously reported in TgCRND8 mice fed with oleuropein aglycone, resulting in comparable neuroprotection.
- Subjects :
- Alzheimer Disease complications
Alzheimer Disease genetics
Amyloid beta-Protein Precursor genetics
Amyloidosis, Familial metabolism
Animals
Autophagy drug effects
Brain pathology
Corneal Dystrophies, Hereditary metabolism
Disease Models, Animal
Glial Fibrillary Acidic Protein metabolism
Maze Learning drug effects
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation genetics
Phenylethyl Alcohol therapeutic use
Presenilin-1 genetics
RNA, Messenger metabolism
Signal Transduction drug effects
Tumor Necrosis Factor-alpha metabolism
Alzheimer Disease pathology
Antioxidants therapeutic use
Brain metabolism
Cognition Disorders diet therapy
Cognition Disorders etiology
Diet
Phenylethyl Alcohol analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8908
- Volume :
- 63
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of Alzheimer's disease : JAD
- Publication Type :
- Academic Journal
- Accession number :
- 29710709
- Full Text :
- https://doi.org/10.3233/JAD-171124