Neurochemical Research

, Volume 43, Issue 9, pp 1766–1778 | Cite as

Association of Induced Hyperhomocysteinemia with Alzheimer’s Disease-Like Neurodegeneration in Rat Cortical Neurons After Global Ischemia-Reperfusion Injury

  • Maria Kovalska
  • Barbara Tothova
  • Libusa Kovalska
  • Zuzana Tatarkova
  • Dagmar Kalenska
  • Anna Tomascova
  • Marian Adamkov
  • Jan LehotskyEmail author
Original Paper


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.


Alzheimer’s disease Homocysteine Brain ischemia β-Amyloid peptide 



This study was supported by Grants VEGA 1/0171/18, VEGA 1/0128/16, APVV 15/0107 from the Ministry of Education of the Slovak Republic, and by project “Identification of novel markers in diagnostic panel of neurological diseases” code: 26220220114, co-financed from EU sources and European Regional Development Fund. The authors are grateful to Mrs. Greta Kondekova and Mrs. Agata Resetarova for their excellent help with immunohistochemical and histological procedures.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Jessenius Faculty of Medicine in Martin, Institute of Histology and EmbryologyComenius University in BratislavaMartinSlovakia
  2. 2.BioMed, Division of Oncology, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia
  3. 3.Jessenius Faculty of Medicine in Martin, Institute of Medical BiochemistryComenius University in BratislavaMartinSlovakia
  4. 4.Jessenius Faculty of Medicine in MartinComenius University in Bratislava, Clinic of Stomatology and Maxillofacial SurgeryMartinSlovakia
  5. 5.BioMed, Division of Neurosciences, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia
  6. 6.Jessenius Faculty of Medicine, Institute of Medical Biochemistry and BioMedComenius UniversityMartinSlovakia

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