PMID- 30003389 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20181231 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 43 IP - 9 DP - 2018 Sep TI - Association of Induced Hyperhomocysteinemia with Alzheimer's Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury. PG - 1766-1778 LID - 10.1007/s11064-018-2592-x [doi] AB - Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder that results in massive hippocampal and neocortical neuronal loss leading to dementia and eventual death. The exact cause of Alzheimer's disease is not fully explored, although a number of risk factors have been recognized, including high plasma concentration of homocysteine (Hcy). Hyperhomocysteinemia (hHcy) is considered a strong, independent risk factor for stroke and dementia. However, the molecular background underlying these mechanisms linked with hHcy and ischemic stroke is not fully understood. Paper describes rat model of global forebrain ischemia combined with the experimentally induced hHcy. Global ischemia-reperfusion injury (IRI) was developed by 4-vessels occlusion lasting for 15 min followed by reperfusion period of 72 h. hHcy was induced by subcutaneous injection of 0.45 micromol/g of Hcy in duration of 14 days. The results showed remarkable neural cell death induced by hHcy in the brain cortex and neurodegeneration is further aggravated by global IRI. We demonstrated degeneration of cortical neurons, alterations in number and morphology of tissue astrocytes and dysregulation of oxidative balance with increased membrane protein oxidation. Complementary to, an immunohistochemical analysis of tau protein and beta-amyloid peptide showed that combination of hHcy with the IRI might lead to the progression of AD-like pathological features. Conclusively, these findings suggest that combination of risk factor hHcy with IRI aggravates neurodegeneration processes and leads to development of AD-like pathology in cerebral cortex. FAU - Kovalska, Maria AU - Kovalska M AD - Jessenius Faculty of Medicine in Martin, Institute of Histology and Embryology, Comenius University in Bratislava, Martin, Slovakia. FAU - Tothova, Barbara AU - Tothova B AD - BioMed, Division of Oncology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. AD - Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia. FAU - Kovalska, Libusa AU - Kovalska L AD - Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Clinic of Stomatology and Maxillofacial Surgery, Martin, Slovakia. FAU - Tatarkova, Zuzana AU - Tatarkova Z AD - Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia. FAU - Kalenska, Dagmar AU - Kalenska D AD - Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia. FAU - Tomascova, Anna AU - Tomascova A AD - Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia. FAU - Adamkov, Marian AU - Adamkov M AD - Jessenius Faculty of Medicine in Martin, Institute of Histology and Embryology, Comenius University in Bratislava, Martin, Slovakia. FAU - Lehotsky, Jan AU - Lehotsky J AUID- ORCID: 0000-0002-2408-5745 AD - Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia. lehotsky@jfmed.uniba.sk. AD - BioMed, Division of Neurosciences, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. lehotsky@jfmed.uniba.sk. AD - Jessenius Faculty of Medicine, Institute of Medical Biochemistry and BioMed, Comenius University, Mala Hora 4D, 036 01, Martin, Slovakia. lehotsky@jfmed.uniba.sk. LA - eng GR - VEGA 128/16/Slovak Grant Agency/ GR - 15/0107/Agentura na Podporu Vyskumu a Vyvoja/ PT - Journal Article DEP - 20180712 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0LVT1QZ0BA (Homocysteine) SB - IM MH - Alzheimer Disease/chemically induced/*pathology MH - Animals MH - Cerebral Cortex/drug effects/*pathology MH - Homocysteine/*toxicity MH - Hyperhomocysteinemia/chemically induced/*pathology MH - Male MH - Nerve Degeneration/chemically induced/*pathology MH - Rats MH - Rats, Wistar MH - Reperfusion Injury/chemically induced/*pathology OTO - NOTNLM OT - Alzheimer's disease OT - Brain ischemia OT - Homocysteine OT - beta-Amyloid peptide EDAT- 2018/07/14 06:00 MHDA- 2019/01/01 06:00 CRDT- 2018/07/14 06:00 PHST- 2018/03/16 00:00 [received] PHST- 2018/07/05 00:00 [accepted] PHST- 2018/06/25 00:00 [revised] PHST- 2018/07/14 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2018/07/14 06:00 [entrez] AID - 10.1007/s11064-018-2592-x [pii] AID - 10.1007/s11064-018-2592-x [doi] PST - ppublish SO - Neurochem Res. 2018 Sep;43(9):1766-1778. doi: 10.1007/s11064-018-2592-x. Epub 2018 Jul 12.