Effects of Modeling of Hypercalcemia and [beta]-Amyloid on Cultured Hippocampal Neurons of Rats

• Published in: Neurophysiology (New York) Vol. 52; no. 5; pp. 348 - 357
• Main Authors: Rozumna, N.M, Shkryl, V.M, Ganzha, V.V, Lukyanetz, E.A
• Format: Journal Article
• Language: English
• Published: Springer 19-08-2021
• Subjects: Advertising executives; Alzheimer's disease; Hypercalcemia; Neurons; Neurophysiology; Penicillin G
• ISSN: 0090-2977; 1573-9007
• DOI: 10.1007/s11062-021-09891-8

Alzheimer's disease (AD) is the most common type of dementia; it is characterized by accumulations of amyloid (A[beta]) plaques and neurofibrillary tangles in the brain. Intracellular [Ca.sup.2+] 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 [Ca.sup.2+] neuronal homeostasis may play an important role in the AD pathogenesis, as impaired [Ca.sup.2+] concentrations can cause synaptic deficiency and contribute to the accumulation of A[beta] 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 A[beta]. Our experiments showed that a high [Ca.sup.2+] level and A[beta] 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 [[Ca.sup.2+]] and A[beta] on intracellular calcium homeostasis in these neurons. As was found under our conditions, modelling of hypercalcemia with 3.0 mM extracellular Ca[Cl.sub.2] in the medium resulted in increase in the basal intracellular [Ca.sup.2+] 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 [Ca.sup.2+] content in the endoplasmic reticulum increased by 20%. Restoration of the [Ca.sup.2+] concentration in the neurons after cell stimulation slowed down considerably. Similar but more intense changes were observed in the neurons cultured with A[beta] and 3.0 mM Ca[Cl.sub.2] 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 [Ca.sup.2+] concentration also increases, and its post-stimulation return to the basal level is slowed down. Considering that extracellular [Ca.sup.2+] 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.