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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1797534994687590400 |
---|---|
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. |
first_indexed | 2024-03-10T11:38:18Z |
format | Article |
id | doaj.art-2a58ba28e09e44e5bb2dfce03bf49a2c |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T11:38:18Z |
publishDate | 2021-05-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT mariakovalska methioninedietevokedhyperhomocysteinemiacauseshippocampalalterationsmetabolomicsplasmachangesandbehavioralpatterninwildtyperats AT evabaranovicova methioninedietevokedhyperhomocysteinemiacauseshippocampalalterationsmetabolomicsplasmachangesandbehavioralpatterninwildtyperats AT dagmarkalenska methioninedietevokedhyperhomocysteinemiacauseshippocampalalterationsmetabolomicsplasmachangesandbehavioralpatterninwildtyperats AT annatomascova methioninedietevokedhyperhomocysteinemiacauseshippocampalalterationsmetabolomicsplasmachangesandbehavioralpatterninwildtyperats AT marianadamkov methioninedietevokedhyperhomocysteinemiacauseshippocampalalterationsmetabolomicsplasmachangesandbehavioralpatterninwildtyperats AT libusakovalska methioninedietevokedhyperhomocysteinemiacauseshippocampalalterationsmetabolomicsplasmachangesandbehavioralpatterninwildtyperats AT janlehotsky methioninedietevokedhyperhomocysteinemiacauseshippocampalalterationsmetabolomicsplasmachangesandbehavioralpatterninwildtyperats |