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Effects of magnesium orotate, benfotiamine and a combination of vitamins on mitochondrial and cholinergic function in the TgF344-AD rat model of Alzheimer's disease
- Glucose hypometabolism, mitochondrial dysfunction, and cholinergic deficits have been reported in early stages of Alzheimer’s disease (AD). Here, we examine these parameters in TgF344-AD rats, an Alzheimer model that carries amyloid precursor protein and presenilin-1 mutations, and of wild type F344 rats. In mitochondria isolated from rat hippocampi, we found reductions of complex I and oxidative phosphorylation in transgenic rats. Further impairments, also of complex II, were observed in aged (wild-type and transgenic) rats. Treatment with a “cocktail” containing magnesium orotate, benfotiamine, folic acid, cyanocobalamin, and cholecalciferol did not affect mitochondrial activities in wild-type rats but restored diminished activities in transgenic rats to wild-type levels. Glucose, lactate, and pyruvate levels were unchanged by age, genetic background, or treatment. Using microdialysis, we also investigated extracellular concentrations of acetylcholine that were strongly reduced in transgenic animals. Again, ACh levels in wild-type rats did not change upon treatment with nutrients, whereas the cocktail increased hippocampal acetylcholine levels under physiological stimulation. We conclude that TgF344-AD rats display a distinct mitochondrial and cholinergic dysfunction not unlike the findings in patients suffering from AD. This dysfunction can be partially corrected by the application of the “cocktail” which is particularly active in aged rats. We suggest that the TgF344-AD rat is a promising model to further investigate mitochondrial and cholinergic dysfunction and potential treatment approaches for AD.
Author: | Christian VielORCiD, Adrian T. BrandtnerORCiD, Alexander Weißhaar, Alina Barbara LehtoGND, Marius FuchsORCiD, Jochen KleinORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-795302 |
DOI: | https://doi.org/10.3390/ph14121218 |
ISSN: | 1424-8247 |
Parent Title (English): | Pharmaceuticals |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/11/24 |
Date of first Publication: | 2021/11/24 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/11/16 |
Tag: | Alzheimer’s disease; TgF344-AD; acetylcholine; complex I; electron transfer system; glucose; hippocampus; lactate; microdialysis; mitochondrial respiration |
Volume: | 14 |
Issue: | 12, art. 1218 |
Article Number: | 1218 |
Page Number: | 20 |
First Page: | 1 |
Last Page: | 20 |
Note: | This study was funded by a grant form Wörwag Pharmaceuticals (grant 0815) and internal funds of Goethe University given to J.K. |
HeBIS-PPN: | 515215988 |
Institutes: | Biochemie, Chemie und Pharmazie |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |