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Effects of Modeling of Hypercalcemia and β-Amyloid on Cultured Hippocampal Neurons of Rats

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Neurophysiology Aims and scope

Alzheimer’s disease (AD) is the most common type of dementia; it is characterized by accumulations of amyloid (Aβ) plaques and neurofibrillary tangles in the brain. Intracellular Ca2+ homeostasis plays an important role in the control of events in the neuronal system, including neurotransmitter release, synaptic plasticity, memory, and neuronal death. Therefore, dysregulation of Ca2+ neuronal homeostasis may play an important role in the AD pathogenesis, as impaired Ca2+ concentrations can cause synaptic deficiency and contribute to the accumulation of Aβ plaques and neurofibrillary tangles. In our in vitro research, we tested the possible involvement of modeled hypercalcemia in the AD development using a hippocampal cell culture treated with Aβ. Our experiments showed that a high Ca2+ level and Aβ in the medium significantly and in a rather similar manner influence hippocampal neuronal viability in the cell culture. These factors decreased the number of alive neurons and intensified apoptotic and necrotic changes. We also compared the effects of the high [Ca2+] and Aβ on intracellular calcium homeostasis in these neurons. As was found under our conditions, modelling of hypercalcemia with 3.0 mM extracellular CaCl2 in the medium resulted in increase in the basal intracellular Ca2+ level in the cultured neurons by 16%, on average, compared to that in the control. The amplitude of calcium responses to depolarization of the cells with 50 mM KCI in the solution increased by 11%, and the Ca2+ content in the endoplasmic reticulum increased by 20%. Restoration of the Ca2+ concentration in the neurons after cell stimulation slowed down considerably. Similar but more intense changes were observed in the neurons cultured with Aβ and 3.0 mM CaCl2 together. The latter effects corresponded to a 17% increase upon applying 50 mM KCl and 22% upon applying 10 mM caf feine solution, compared to those in the control cells group. Thus, under a rise in the extracellular calcium concentration, the intracellular Ca2+ concentration also increases, and its post-stimulation return to the basal level is slowed down. Considering that extracellular Ca2+ dysregulation can be readily involved in the AD pathogenesis, it is likely that the correction of this dysregulation may serve as a potential therapeutic approach for the prevention and/or treatment of AD.

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Authors and Affiliations

  1. Department of Biophysics of Ion Channels, Bogomolets Institute of Physiology, NAS of Ukraine, Kyiv, Ukraine

    N. M. Rozumna, V. M. Shkryl, V. V. Ganzha & E. A. Lukyanetz

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  1. N. M. Rozumna
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  2. V. M. Shkryl
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  3. V. V. Ganzha
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  4. E. A. Lukyanetz
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Correspondence to E. A. Lukyanetz.

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Rozumna, N.M., Shkryl, V.M., Ganzha, V.V. et al. Effects of Modeling of Hypercalcemia and β-Amyloid on Cultured Hippocampal Neurons of Rats. Neurophysiology 52, 348–357 (2020). https://doi.org/10.1007/s11062-021-09891-8

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  • DOI: https://doi.org/10.1007/s11062-021-09891-8

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