TY  - JOUR
A1  - Viel, Christian
A1  - Brandtner, Adrian T.
A1  - Weißhaar, Alexander
A1  - Lehto, Alina Barbara
A1  - Fuchs, Marius
A1  - Klein, Jochen
T1  - 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
T2  - Pharmaceuticals
N2  - 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.
KW  - acetylcholine
KW  - Alzheimer’s disease
KW  - microdialysis
KW  - glucose
KW  - lactate
KW  - mitochondrial respiration
KW  - complex I
KW  - electron transfer system
KW  - TgF344-AD
KW  - hippocampus
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/79530
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-795302
SN  - 1424-8247
N1  - This study was funded by a grant form Wörwag Pharmaceuticals (grant 0815) and internal funds of Goethe University given to J.K.
VL  - 14
IS  - 12, art. 1218
SP  - 1
EP  - 20
PB  - MDPI
CY  - Basel
ER  -