PMID- 34066973 OWN - NLM STAT- MEDLINE DCOM- 20210616 LR - 20240226 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 9 DP - 2021 May 7 TI - Methionine Diet Evoked Hyperhomocysteinemia Causes Hippocampal Alterations, Metabolomics Plasma Changes and Behavioral Pattern in Wild Type Rats. LID - 10.3390/ijms22094961 [doi] LID - 4961 AB - 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. FAU - Kovalska, Maria AU - Kovalska M AUID- ORCID: 0000-0001-6802-5309 AD - Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. FAU - Baranovicova, Eva AU - Baranovicova E AD - Department of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. FAU - Kalenska, Dagmar AU - Kalenska D AD - Department of Anatomy, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. FAU - Tomascova, Anna AU - Tomascova A AD - Department of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. FAU - Adamkov, Marian AU - Adamkov M AD - Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. FAU - Kovalska, Libusa AU - Kovalska L AD - Clinic of Stomatology and Maxillofacial Surgery, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. FAU - Lehotsky, Jan AU - Lehotsky J AD - Department of Neuroscience, Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. AD - Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia. LA - eng GR - 230/20/Vedecka Grantova Agentura MSVVaS SR a SAV/ GR - 15/107/Agentura na Podporu Vyskumu a Vyvoja/ PT - Journal Article DEP - 20210507 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0LVT1QZ0BA (Homocysteine) RN - AE28F7PNPL (Methionine) SB - IM MH - Animals MH - *Behavior, Animal MH - Hippocampus/*pathology MH - Homocysteine/blood MH - Hyperhomocysteinemia/*blood/*metabolism/pathology MH - In Situ Nick-End Labeling MH - Magnetic Resonance Spectroscopy MH - Male MH - *Metabolomics MH - Methionine MH - Rats, Wistar MH - Staining and Labeling MH - Rats PMC - PMC8124831 OTO - NOTNLM OT - hyperhomocysteinemia OT - methionine diet OT - morris water maze OT - neurodegeneration OT - wild-type rats COIS- The authors declare no conflict of interest. EDAT- 2021/06/03 06:00 MHDA- 2021/06/17 06:00 PMCR- 2021/05/07 CRDT- 2021/06/02 01:17 PHST- 2021/03/18 00:00 [received] PHST- 2021/04/12 00:00 [revised] PHST- 2021/05/03 00:00 [accepted] PHST- 2021/06/02 01:17 [entrez] PHST- 2021/06/03 06:00 [pubmed] PHST- 2021/06/17 06:00 [medline] PHST- 2021/05/07 00:00 [pmc-release] AID - ijms22094961 [pii] AID - ijms-22-04961 [pii] AID - 10.3390/ijms22094961 [doi] PST - epublish SO - Int J Mol Sci. 2021 May 7;22(9):4961. doi: 10.3390/ijms22094961.