Alzheimer’s disease (AD) is a widespread chronic neurodegenerative pathology characterized by synaptic dysfunction, partial neuronal death, cognitive decline and memory impairments. The major hallmarks of AD are extracellular senile amyloid plaques formed by various types of amyloid proteins (Aβ) and the formation and accumulation of intracellular neurofibrillary tangles. However, there is a lack of relevant experimental models for studying changes in neural network activity, the features of intercellular signaling or the effects of drugs on the functional activity of nervous cells during AD development. In this work, we examined two experimental models of amyloidopathy using primary hippocampal cultures. The first model involves the embryonic brains of 5xFAD mice; the second uses chronic application of amyloid beta 1-42 (Aβ1-42). The model based on primary hippocampal cells obtained from 5xFAD mice demonstrated changes in spontaneous network calcium activity characterized by a decrease in the number of cells exhibiting Ca²⁺ activity, a decrease in the number of Ca²⁺ oscillations and an increase in the duration of Ca²⁺ events from day 21 of culture development in vitro. Chronic application of Aβ1-42 resulted in the rapid establishment of significant neurodegenerative changes in primary hippocampal cultures, leading to marked impairments in neural network calcium activity and increased cell death. Using this model and multielectrode arrays, we studied the influence of amyloidopathy on spontaneous bioelectrical neural network activity in primary hippocampal cultures. It was shown that chronic Aβ application decreased the number of network bursts and spikes in a burst. The spatial structure of neural networks was also disturbed that characterized by reduction in both the number of key network elements (hubs) and connections between network elements. Moreover, application of brain-derived neurotrophic factor (BDNF) recombinant protein and BDNF hyperexpression by an adeno-associated virus vector partially prevented these amyloidopathy-induced neurodegenerative phenomena. BDNF maintained cell viability and spontaneous bioelectrical and calcium network activity in primary hippocampal cultures.

阿尔茨海默氏病（AD）是一种广泛的慢性神经退行性病变，其特征在于突触功能障碍，部分神经元死亡，认知能力下降和记忆障碍。AD的主要特征是由各种类型的淀粉样蛋白（Aβ）形成的细胞外老年淀粉样斑块以及细胞内神经原纤维缠结的形成和积累。然而，缺乏相关的实验模型来研究神经网络活动的变化，细胞间信号的特征或药物对AD发展过程中神经细胞功能活性的影响。在这项工作中，我们检查了使用原代海马培养物的两种淀粉样变性实验模型。第一个模型涉及5xFAD小鼠的胚胎脑。第二种是长期使用淀粉样蛋白1-1-4（Aβ1-42）。从培养开始的第21天起²⁺活性，Ca ²⁺振荡次数减少和Ca ²⁺事件持续时间增加体外。长期应用Aβ1-42可在原代海马培养物中迅速建立明显的神经退行性改变，从而导致神经网络钙活性明显受损并增加细胞死亡。使用此模型和多电极阵列，我们研究了淀粉样变性对原代海马培养物中自发生物电神经网络活动的影响。结果表明，长期使用Aβ可以减少网络突发次数和突发次数。神经网络的空间结构也受到干扰，其特点是减少了关键网络元素（集线器）的数量以及网络元素之间的连接。此外，腺相关病毒载体应用脑源性神经营养因子（BDNF）重组蛋白和BDNF高表达部分预防了这些淀粉样变性病引起的神经变性现象。BDNF在原代海马培养物中维持细胞活力以及自发的生物电和钙网络活性。