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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2021; 67(2): 3-10

Effect of memantine on calcium signaling in hippocampal neurons cultured with β-amyloid

V.M. Shkryl, V.V. Ganzha, E.A. Lukyanetz

    O.O. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv


Alzheimer’s disease (AD) is the most common type of dementia and is characterized by accumulating amyloid (Aβ) plaques and neurofibrillary tangles in the brain. Excessive stimulation of glutamate receptors, mainly NMDA-type, causes intense entry of calcium ions into cells and is a key early step in glutamateinduced excitotoxicity, resulting in many neurological diseases, including AD. Memantine, an NMDA receptor antagonist, blocks NMDA receptors and reduce the influx of calcium ions into neuron. In our experiments, we have modeled AD on cultured rat hippocampal neurons to test the effects of memantine on calcium signaling in neurons. Our results show that the neuroprotective effect of memantine could be provided not only through the inhibition of NMDA receptor current but also through the suppression of voltage-dependent Ca2+ channels, most likely L-type. This study suggests that NMDA receptor antagonist memantine can protect hippocampal neurons from calcium overloading induced by Aβ1–42 amyloid exposure via blocking Ca2+ channels

Keywords: hippocampal neuron culture; Aβ-amyloid; NMDA; memantine; calcium; calcium homeostasis; Alzheimer’s disease


  1. Prasansuklab A, Tencomnao T. Amyloidosis in Alzheimer's disease: The toxicity of amyloid beta (Aβ), mechanisms of its accumulation and implications of medicinal plants for therapy. Evid Based Complement Alternat Med. 2013;2013:413808. CrossRef PubMed PubMedCentral
  2. Tyshchenko YN, Lukyanetz EA. The role of betaamyloid in norm and at Alzheimer's disease. Fiziol Zh. 2020;66(6):88-96. CrossRef
  3. Kravenska Y, Nieznanska H, Nieznanski K, Lukyanetz E, Szewczyk A, Koprowski P. The monomers, oligomers, and fibrils of amyloid-β inhibit the activity of mitoBKCa channels by a membrane-mediated mechanism. Biochimica et Biophysica Acta (BBA) - Biomembranes. 2020;1862(9):183337. CrossRef PubMed
  4. Pchitskaya E, Popugaeva E, Bezprozvanny I. Calcium signaling and molecular mechanisms underlying neurodegenerative diseases. Cell Calcium. 2018;70:87-94. CrossRef PubMed PubMedCentral
  5. Khachaturian ZS. Hypothesis on the regulation of cytosol calcium concentration and the aging brain. Neurobiol Aging. 1987;8(4):345-6. CrossRef
  6. Demuro A, Parker I, Stutzmann GE. Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem. 2010;285(17):12463-8. CrossRef PubMed PubMedCentral
  7. Kostyk PG, Kostyuk E, Lukyanetz EA. Calcium ions in brain function - from physiology to pathology. Kyiv: Naukova Dumka; 2005. 152 p.
  8. Kostyk PG, Kostyuk EP, Lukyanetz EA. Intracellular calcium signaling - structures and functions. Kyiv: Naukova Dumka; 2010. 176 p.
  9. Kostyuk PG, Lukyanetz EA. Intracellular calcium signaling - basic mechanisms and possible alterations. In: Ayrapetyan SN, Markov MS, editors. Bioelectromagnetics Current Concepts. NATO Security Through Science Series. Netherlands: Springer 2006. p. 87-122. CrossRef
  10. McShane R, Westby MJ, Roberts E, Minakaran N, Schneider L, Farrimond LE, et al. Memantine for dementia. Cochrane Database System Reviews. 2019; 3(3):Cd003154. CrossRef PubMedCentral
  11. Peng D, Yuan X, Zhu R. Memantine hydrochloride in the treatment of dementia subtypes. J Clin Neurosci. 2013;20(11):1482-5. CrossRef PubMed
  12. Gorbachenko VA, Lukyanetz EA. Effects of memantine on the passive avoidance test in young rats. Fiziol Zh (Kiev, Ukraine : 1994). 2020;66(5):3-10. CrossRef
  13. Tyshchenko Y, Lukyanetz EA. Effects of memantine on behavioral indices of rats in the open field. Neurophysiology. 2017;49(6):453-7. CrossRef
  14. Gorbachenko VA, Kruchenko JO, Chereda IS, Lukyanetz EA. Measurements of the time parameters of conditioned food reflex in rats under memantin treatment with using of automatic registration system. Bull Taras Shevchenko Nat Univ Kyiv Ser: Radiophysics and Electronics. 2015;1(23):23-6.
  15. Kruchenko ZA, Gorbachenko VA, Chereda IS, Lukyanetz EA. Effect of memantine on motor behavioral phenomena in rats of different ages. Neurophysiology. 2014;46(5):448-51. CrossRef
  16. Kravenska EV, Chopovska VV, Yavorskaya EN, Lukyanetz EA. The role of mitochondria in the development of Alzheimer's disease. Tavrichesky MedBiol Bull. 2012;15(3/2):147-9.
  17. Kravenska EV, Ganzha VV, Yavorskaya EN, Lukyanetz EA. Effect of cyclosporin a on the viability of hippocampal cells cultured under conditions of modeling of Alzheimer's disease. Neurophysiology. 2016;48(4):246-51. CrossRef
  18. Beesley S, Olcese J, Saunders C, Bienkiewicz EA. Combinatorial treatment effects in a cell culture model of Alzheimer's disease. J Alzheimers Dis. 2017;55(3):1155-66. CrossRef PubMed
  19. Dubey SK, Ram MS, Krishna KV, Saha RN, Singhvi G, Agrawal M, et al. Recent expansions on cellular models to uncover the scientific barriers towards drug development for Alzheimer's disease. Cell Mo Neurobiol. 2019;39(2):181-209. CrossRef PubMed
  20. Shkryl VM, Maxwell JT, Domeier TL, Blatter LA. Refractoriness of sarcoplasmic reticulum Ca2+ release determines Ca2+ alternans in atrial myocytes. Am J PhysiolHeart Circulat Physiol. 2012;302(11):H2310-H20. CrossRef PubMed PubMedCentral
  21. Shkryl VM, Kostyuk PG, Lukyanetz EA. Dual action of cytosolic calcium on calcium channel activity during hypoxia in hippocampal neurones. NeuroReport. 2001;12(18):4035-9. CrossRef PubMed
  22. Shkryl VM, Nikolaenko LM, Kostyuk PG, Lukyanetz EA. High-threshold calcium channel activity in rat hippocampal neurones during hypoxia. Brain Res. 1999;833(2):319-28. CrossRef
  23. Shkryl VM. Error correction due to background subtraction in ratiometric calcium measurements with CCD camera. Heliyon. 2020;6(6):e04180. CrossRef PubMed PubMedCentral
  24. Olivares D, Deshpande VK, Shi Y, Lahiri DK, Greig NH, Rogers JT, et al. N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer's disease, vascular dementia and Parkinson's disease. Current Alzheimer Res. 2012;9(6):746-58. CrossRef PubMed
  25. Zipfel GJ, Babcock DJ, Lee JM, Choi DW. Neuronal apoptosis after CNS injury: the roles of glutamate and calcium. J Neurotrauma. 2000;17(10):857-69. CrossRef PubMed
  26. Danysz W, Parsons CG. Alzheimer's disease, β-amyloid, glutamate, NMDA receptors and memantine - searching for the connections. Brit J Pharmacol. 2012;167(2): 324-52. CrossRef PubMed PubMedCentral
  27. Mycielska ME, Djamgoz MB. Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease. J Cell Sci. 2004;117(Pt 9):1631-9. CrossRef PubMed
  28. Baginskas A, Kuras A, Grigaliūnas A. Inhibition of dendritic L-type calcium current by memantine in frog tectum. Medicina (Kaunas, Lithuania). 2013;49(9):409-14. CrossRef

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