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
DOI: https://doi.org/10.15407/fz67.02.003
![](/images/cite.png)
Abstract
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
References
- 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
- Tyshchenko YN, Lukyanetz EA. The role of betaamyloid in norm and at Alzheimer's disease. Fiziol Zh. 2020;66(6):88-96.
CrossRef
- 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
- Pchitskaya E, Popugaeva E, Bezprozvanny I. Calcium signaling and molecular mechanisms underlying neurodegenerative diseases. Cell Calcium. 2018;70:87-94.
CrossRef
PubMed PubMedCentral
- Khachaturian ZS. Hypothesis on the regulation of cytosol calcium concentration and the aging brain. Neurobiol Aging. 1987;8(4):345-6.
CrossRef
- 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
- Kostyk PG, Kostyuk E, Lukyanetz EA. Calcium ions in brain function - from physiology to pathology. Kyiv: Naukova Dumka; 2005. 152 p.
- Kostyk PG, Kostyuk EP, Lukyanetz EA. Intracellular calcium signaling - structures and functions. Kyiv: Naukova Dumka; 2010. 176 p.
- 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
- 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
- Peng D, Yuan X, Zhu R. Memantine hydrochloride in the treatment of dementia subtypes. J Clin Neurosci. 2013;20(11):1482-5.
CrossRef
PubMed
- 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
- Tyshchenko Y, Lukyanetz EA. Effects of memantine on behavioral indices of rats in the open field. Neurophysiology. 2017;49(6):453-7.
CrossRef
- 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.
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- Shkryl VM. Error correction due to background subtraction in ratiometric calcium measurements with CCD camera. Heliyon. 2020;6(6):e04180.
CrossRef
PubMed PubMedCentral
- 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
- 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
- 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
- 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
- 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
|