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Association of Induced Hyperhomocysteinemia with Alzheimer's Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury.
Neurochem Res. 2018 Sep; 43(9):1766-1778.NR

Abstract

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 µmol/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 β-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.

Authors+Show Affiliations

Jessenius Faculty of Medicine in Martin, Institute of Histology and Embryology, Comenius University in Bratislava, Martin, Slovakia.BioMed, Division of Oncology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia.Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Clinic of Stomatology and Maxillofacial Surgery, Martin, Slovakia.Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia.Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia.Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia.Jessenius Faculty of Medicine in Martin, Institute of Histology and Embryology, Comenius University in Bratislava, Martin, Slovakia.Jessenius Faculty of Medicine in Martin, Institute of Medical Biochemistry, Comenius University in Bratislava, Martin, Slovakia. lehotsky@jfmed.uniba.sk. BioMed, Division of Neurosciences, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. lehotsky@jfmed.uniba.sk. Jessenius Faculty of Medicine, Institute of Medical Biochemistry and BioMed, Comenius University, Mala Hora 4D, 036 01, Martin, Slovakia. lehotsky@jfmed.uniba.sk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30003389

Citation

Kovalska, Maria, et al. "Association of Induced Hyperhomocysteinemia With Alzheimer's Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury." Neurochemical Research, vol. 43, no. 9, 2018, pp. 1766-1778.
Kovalska M, Tothova B, Kovalska L, et al. Association of Induced Hyperhomocysteinemia with Alzheimer's Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury. Neurochem Res. 2018;43(9):1766-1778.
Kovalska, M., Tothova, B., Kovalska, L., Tatarkova, Z., Kalenska, D., Tomascova, A., Adamkov, M., & Lehotsky, J. (2018). Association of Induced Hyperhomocysteinemia with Alzheimer's Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury. Neurochemical Research, 43(9), 1766-1778. https://doi.org/10.1007/s11064-018-2592-x
Kovalska M, et al. Association of Induced Hyperhomocysteinemia With Alzheimer's Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury. Neurochem Res. 2018;43(9):1766-1778. PubMed PMID: 30003389.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Induced Hyperhomocysteinemia with Alzheimer's Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury. AU - Kovalska,Maria, AU - Tothova,Barbara, AU - Kovalska,Libusa, AU - Tatarkova,Zuzana, AU - Kalenska,Dagmar, AU - Tomascova,Anna, AU - Adamkov,Marian, AU - Lehotsky,Jan, Y1 - 2018/07/12/ PY - 2018/03/16/received PY - 2018/07/05/accepted PY - 2018/06/25/revised PY - 2018/7/14/pubmed PY - 2019/1/1/medline PY - 2018/7/14/entrez KW - Alzheimer’s disease KW - Brain ischemia KW - Homocysteine KW - β-Amyloid peptide SP - 1766 EP - 1778 JF - Neurochemical research JO - Neurochem Res VL - 43 IS - 9 N2 - 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 µmol/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 β-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. SN - 1573-6903 UR - https://www.unboundmedicine.com/medline/citation/30003389/Association_of_Induced_Hyperhomocysteinemia_with_Alzheimer's_Disease_Like_Neurodegeneration_in_Rat_Cortical_Neurons_After_Global_Ischemia_Reperfusion_Injury_ L2 - https://doi.org/10.1007/s11064-018-2592-x DB - PRIME DP - Unbound Medicine ER -