Ganzha V. Influence of neuroprotective and damaging factors on hippocampal neurons under the action of beta-amyloid

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and memory loss. The pathogenesis of AD is complex, depends on many factors and is still not fully understood. Extracellular deposits of β -amyloid (Aβ) peptide in the form of senile plaques, the formation of intracellular neurofibrillary tangles and massive neuronal loss, especially in the hippocampus, are considered the main pathological signs of AD. The hippocampus is known to be responsible for learning, short-term memory, and a number of other processes. During the development of HA, up to 80% of the neurons in the hippocampus die and it becomes increasingly difficult for a person to absorb new information and remember events. The aim of this study was to elucidate the effects of some neuroprotective and damaging factors on rat hippocampal neurons when exposed to Aβ1–42 to determine the possible mechanism of action of this agent in modeling Alzheimer’s disease. Using fluorescence microscopy, it was found that Aβ1-42-amyloid causes an increase in the concentration of intracellular Ca2 + in the neurons of the culture. Both Ca2 + input and its redistribution increase with increasing Ca2 + content in the endoplasmic reticulum. As a result, the basal level of Ca2+ increases, which negatively affects the viability of neurons. Confocal microscopy was the first to study the effect of memantine, cyclosporine A, and cerium dioxide nanoparticles on the viability of hippocampal culture neurons cultured with Aβ1–42-amyloid, with the possibility of establishing their neuroprotective properties. The protective properties of the non-competitive low-affinity antagonist NMDA - memantine receptors on the viability of neurons in the hippocampus of rats under the influence of Aβ1-42-amyloid were studied. Memantine showed a protective effect under experimental conditions of excitotoxicity caused by the addition of NMDA to the culture medium. Blocking the opening of mitochondrial pores of nonspecific permeability with cyclosporine A, helped to reduce the number of necrotic neurons in the hippocampus with the toxic action of Aβ1-42-amyloid. During the analysis of the data, it was found for the first time that the introduction of cerium dioxide nanoparticles (NDC) significantly reduces the number of neurons killed by Aβ1-42-amyloid, so the use of NDC for biomedical applications is very promising. The data obtained can be the basis for the development of new effective pharmacological approaches to reduce the level and effects of Aβ-amyloid in Alzheimer's disease.