Deciphering the calcium dynamics of a fractional order Alzheimer’s disease model in astrocytes and their networks

IF 7.5 1区 计算机科学 Q1 COMPUTER SCIENCE, ARTIFICIAL INTELLIGENCE Expert Systems with Applications Pub Date : 2025-03-10 DOI:10.1016/j.eswa.2025.126861
Debasish Pradhan, Ranjit Kumar Upadhyay
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引用次数: 0

Abstract

Exposure of astrocytes to amyloid beta (Aβ) is believed to trigger the dysregulation of intracellular calcium ([C]i) oscillations. This study explores a fractional-order model of Aβ-directed astrocytic [C]i dynamics, focusing on multi-pathway flux contributions, stability, and solution properties. The complex behaviors of the model system are explained under three parameter regimes by incorporating an additional external current (Iext) in voltage-gated calcium channels. These behaviors include quiescent states, periodic spiking, and mixed-mode oscillations (MMOs), describing the memory effect of aberrant calcium signaling. Additionally, the bifurcation analysis of [C]i with Aβ level and Iext reveals that amyloid beta substantially induces the calcium oscillation and provides insight into why spontaneous astrocytic [C]i oscillations appear and disappear. Further, a coupled model of astrocytes with fractional order is introduced through linear and nonlinear gap junctions in intercellular diffusion of IP3 and then extended to a network model to study the synchronized firing activities. We demonstrate that for a coupled system with differing fractional-order coefficients (αβ), as the coupling strength F increases, the system with linear coupling can achieve complete synchronization for a higher value of F. In contrast, nonlinear coupling fails to synchronize at the same strength, indicating the complexity of the underlying system dynamics. For a network model with linear coupling, we observe that at F=20 and 110, the system displays evidence of synchronized behavior. These results highlight that linear gap junctions with weak coupling could potentially explain the intricate intracellular oscillations observed during wave propagation in astrocyte networks, which has implications for neurodegenerative diseases like Alzheimer’s.
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来源期刊
Expert Systems with Applications
Expert Systems with Applications 工程技术-工程:电子与电气
CiteScore
13.80
自引率
10.60%
发文量
2045
审稿时长
8.7 months
期刊介绍: Expert Systems With Applications is an international journal dedicated to the exchange of information on expert and intelligent systems used globally in industry, government, and universities. The journal emphasizes original papers covering the design, development, testing, implementation, and management of these systems, offering practical guidelines. It spans various sectors such as finance, engineering, marketing, law, project management, information management, medicine, and more. The journal also welcomes papers on multi-agent systems, knowledge management, neural networks, knowledge discovery, data mining, and other related areas, excluding applications to military/defense systems.
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