title: Neuronal marker recovery after Simvastatin treatment in dementia in the rat brain: in vivo magnetic resonance study.
abstract: The aim of study was to search for new biomarkers with a magnetic resonance technique to identify the early stages of dementia, induced by D-galactose, and evaluate Simvastatin therapy. Localized proton magnetic resonance spectroscopy measurements showed a significant decrease in the concentration of N-acetylaspartate+N-acetylaspartylglutamate and myo-inositol in the D-galactose group compared to the control group, and, conversely, an increase of N-acetylaspartate+N-acetylaspartylglutamate in the D-galactose/Simvastatin group. Using a saturation transfer experiment, with phosphorus magnetic resonance spectroscopy, we observed a significant elevation of the forward rate constant of the creatine kinase reaction in the brains of the D-galactose group compared to controls, and subsequently, a significant reduction of this reaction in the D-galactose/Simvastatin group. Spatial learning and memory were evaluated using the modified Morris water maze test. The dynamics of the learning process represented by the learning index revealed a significant reduction in learning in the D-galactose group, but the deficits as a consequence of the D-galactose effects were recovered in the D-galactose/Simvastatin group, in which the learning dynamics resembled those of the control group. By determining the thiobarbituric acid reactive substances and total coenzyme Q9 in plasma, we have shown that long-term administration of D-galactose created conditions for oxidative stress, and that the administration of Simvastatin decreased oxidative stress in plasma. Volumetry analyses from the hippocampal area show a reduction in the segmented area in the D-galactose group, compared with the control group, and an enlarged area in the hippocampus in the d-galactose/Simvastatin group.
authors.affiliation: Slovak University of Technology in Bratislava, Faculty of Chemical and Food Technology, Institute of Analytical Chemistry, Bratislava, Slovak Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Tušková
authors.affiliation: Slovak Academy of Sciences, Institute of Experimental Pharmacology & Toxicology, Bratislava, Slovak Republic.
authors.forename: Boris
authors.initials: B
authors.lastname: Lipták
authors.affiliation: High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Austria.
authors.forename: Pavol
authors.initials: P
authors.lastname: Szomolányi
authors.affiliation: Comenius University in Bratislava, Medical Faculty, Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Bratislava, Slovak Republic.
authors.forename: Oľga
authors.initials: O
authors.lastname: Vančová
authors.affiliation: Comenius University in Bratislava, Medical Faculty, Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Bratislava, Slovak Republic.
authors.forename: Oľga
authors.initials: O
authors.lastname: Uličná
authors.affiliation: Comenius University in Bratislava, Medical Faculty, Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Bratislava, Slovak Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sumbalová
authors.affiliation: Comenius University in Bratislava, Medical Faculty, Pharmacobiochemical Laboratory of 3rd Department of Internal Medicine, Bratislava, Slovak Republic.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Kucharská
authors.affiliation: Slovak Academy of Sciences, Institute of Experimental Pharmacology & Toxicology, Bratislava, Slovak Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Dubovický
authors.affiliation: High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Austria.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Trattnig
authors.affiliation: Slovak University of Technology in Bratislava, Faculty of Chemical and Food Technology, Institute of Analytical Chemistry, Bratislava, Slovak Republic.
authors.forename: Tibor
authors.initials: T
authors.lastname: Liptaj
authors.affiliation: Slovak University of Technology in Bratislava, Faculty of Chemical and Food Technology, Institute of Analytical Chemistry, Bratislava, Slovak Republic. Electronic address: svatava.kasparova@gmail.com.
authors.forename: Svatava
authors.initials: S
authors.lastname: Kašparová
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D003704:Dementia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004151:Dipeptides / Q000378:metabolism; D004195:Disease Models, Animal; D005690:Galactose; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018697:Nootropic Agents / Q000494:pharmacology*; D009929:Organ Size; D010759:Phosphorus Isotopes; D011522:Protons; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*; D065853:Spatial Learning / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016896:Treatment Outcome; D014451:Ubiquinone / Q000097:blood
chemical_list: D015415:Biomarkers; D004151:Dipeptides; D018697:Nootropic Agents; D010759:Phosphorus Isotopes; D011522:Protons; D017392:Thiobarbituric Acid Reactive Substances; D014451:Ubiquinone; C027172:isospaglumic acid; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D019821:Simvastatin; C030571:ubiquinone 9; D005690:Galactose
keywords: Aging; Animal model; Metabolites; Simvastatin; d-Galactose