Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats

L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocystein...

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Main Authors: Maria Kovalska, Eva Baranovicova, Dagmar Kalenska, Anna Tomascova, Marian Adamkov, Libusa Kovalska, Jan Lehotsky
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/9/4961
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author Maria Kovalska
Eva Baranovicova
Dagmar Kalenska
Anna Tomascova
Marian Adamkov
Libusa Kovalska
Jan Lehotsky
author_facet Maria Kovalska
Eva Baranovicova
Dagmar Kalenska
Anna Tomascova
Marian Adamkov
Libusa Kovalska
Jan Lehotsky
author_sort Maria Kovalska
collection DOAJ
description L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons’ vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in “methylation index” of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.
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spelling doaj.art-2a58ba28e09e44e5bb2dfce03bf49a2c2023-11-21T18:38:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01229496110.3390/ijms22094961Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type RatsMaria Kovalska0Eva Baranovicova1Dagmar Kalenska2Anna Tomascova3Marian Adamkov4Libusa Kovalska5Jan Lehotsky6Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, SlovakiaDepartment of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, SlovakiaDepartment of Anatomy, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, SlovakiaDepartment of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, SlovakiaDepartment of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, SlovakiaClinic of Stomatology and Maxillofacial Surgery, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, SlovakiaDepartment of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, SlovakiaL-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons’ vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in “methylation index” of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.https://www.mdpi.com/1422-0067/22/9/4961methionine diethyperhomocysteinemiamorris water mazeneurodegenerationwild-type rats
spellingShingle Maria Kovalska
Eva Baranovicova
Dagmar Kalenska
Anna Tomascova
Marian Adamkov
Libusa Kovalska
Jan Lehotsky
Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats
International Journal of Molecular Sciences
methionine diet
hyperhomocysteinemia
morris water maze
neurodegeneration
wild-type rats
title Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats
title_full Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats
title_fullStr Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats
title_full_unstemmed Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats
title_short Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats
title_sort methionine diet evoked hyperhomocysteinemia causes hippocampal alterations metabolomics plasma changes and behavioral pattern in wild type rats
topic methionine diet
hyperhomocysteinemia
morris water maze
neurodegeneration
wild-type rats
url https://www.mdpi.com/1422-0067/22/9/4961
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