PMID- 37626897 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20230829 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 12 IP - 16 DP - 2023 Aug 17 TI - Alzheimer's Disease-like Pathological Features in the Dorsal Hippocampus of Wild-Type Rats Subjected to Methionine-Diet-Evoked Mild Hyperhomocysteinaemia. LID - 10.3390/cells12162087 [doi] LID - 2087 AB - Multifactorial interactions, including nutritional state, likely participate in neurodegeneration's pathogenesis and evolution. Dysregulation in methionine (Met) metabolism could lead to the development of hyperhomocysteinaemia (hHcy), playing an important role in neuronal dysfunction, which could potentially lead to the development of Alzheimer's disease (AD)-like pathological features. This study combines proton magnetic resonance spectroscopy ((1)H MRS) with immunohistochemical analysis to examine changes in the metabolic ratio and histomorphological alterations in the dorsal rat hippocampus (dentate gyrus-DG) subjected to a high Met diet. Male Wistar rats (420-480 g) underwent hHcy evoked by a Met-enriched diet (2 g/kg of weight/day) lasting four weeks. Changes in the metabolic ratio profile and significant histomorphological alterations have been found in the DG of hHcy rats. We have detected increased morphologically changed neurons and glial cells with increased neurogenic markers and apolipoprotein E positivity parallel with a diminished immunosignal for the N-Methyl-D-Aspartate receptor 1 in hHcy animals. A Met diet induced hHcy, likely via direct Hcy neurotoxicity, an interference with one carbon unit metabolism, and/or epigenetic regulation. These conditions lead to the progression of neurodegeneration and the promotion of AD-like pathological features in the less vulnerable hippocampal DG, which presents a plausible therapeutic target. 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 - Hnilicova, Petra AU - Hnilicova P AUID- ORCID: 0000-0003-1529-1675 AD - 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 - 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 - 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 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230817 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - AE28F7PNPL (Methionine) RN - 73JWT2K6T3 (Racemethionine) SB - IM MH - Male MH - Rats MH - Animals MH - Methionine MH - *Alzheimer Disease MH - Epigenesis, Genetic MH - Rats, Wistar MH - Racemethionine MH - Diet MH - Hippocampus MH - *Hyperhomocysteinemia PMC - PMC10453870 OTO - NOTNLM OT - 1H MRS OT - Alzheimer's disease-like pathology OT - dorsal hippocampus OT - methionine diet OT - neurodegeneration OT - rat COIS- The authors declare no conflict of interest. EDAT- 2023/08/26 10:45 MHDA- 2023/08/28 07:16 PMCR- 2023/08/17 CRDT- 2023/08/26 01:02 PHST- 2023/06/16 00:00 [received] PHST- 2023/07/27 00:00 [revised] PHST- 2023/08/16 00:00 [accepted] PHST- 2023/08/28 07:16 [medline] PHST- 2023/08/26 10:45 [pubmed] PHST- 2023/08/26 01:02 [entrez] PHST- 2023/08/17 00:00 [pmc-release] AID - cells12162087 [pii] AID - cells-12-02087 [pii] AID - 10.3390/cells12162087 [doi] PST - epublish SO - Cells. 2023 Aug 17;12(16):2087. doi: 10.3390/cells12162087.