Neuronal Resilience and Calcium Signaling Pathways in the Context of Synapse Loss and Calcium Leaks: A Computational MODELING Study and Implications for Alzheimer’s Disease

IF 1.9 4区数学 Q1 MATHEMATICS, APPLIED

SIAM Journal on Applied Mathematics Pub Date : 2023-12-05 DOI:10.1137/23m1557842

Piyush R. Borole, James M. Rosado, MeiRose Neal, Gillian Queisser

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引用次数: 0

Abstract

SIAM Journal on Applied Mathematics, Volume 83, Issue 6, Page 2418-2442, December 2023.
Abstract. In this paper, a coupled electro-calcium model was developed and implemented to computationally explore the effects of neuronal synapse loss, in particular in the context of Alzheimer’s disease. Established parameters affected by Alzheimer’s disease, such as synapse loss, calcium leaks at deteriorating synaptic contacts, and downregulation of the calcium buffer calbindin, are subject to this study. Reconstructed neurons are used to define the computational domain for a system of PDEs and ODEs, discretized by finite differences and solved with a semi-implicit second-order time integrator. The results show neuronal resilience during synapse loss. When incorporating calcium leaks at affected synapses, neurons lose their ability to produce synapse-to-nucleus calcium signals, necessary for learning, plasticity, and neuronal survival. Downregulation of calbindin concentrations partially recovers the signaling pathway to the cell nucleus. These results could define future research pathways toward stabilizing the calcium signaling pathways during Alzheimer’s disease. The coupled electro-calcium model was implemented and solved using MATLAB https://github.com/NeuroBox3D/CalcSim.

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突触丢失和钙泄漏背景下的神经元弹性和钙信号通路:阿尔茨海默病的计算模型研究和意义

SIAM应用数学学报，83卷，第6期，2418-2442页，2023年12月。摘要。本文开发并实现了一个耦合电钙模型，以计算探索神经元突触丢失的影响，特别是在阿尔茨海默病的背景下。受阿尔茨海默病影响的既定参数，如突触丢失、突触接触恶化时的钙泄漏以及钙缓冲物钙结合蛋白的下调，都是本研究的主题。重构神经元用于定义由偏微分方程和偏微分方程组成的系统的计算域，用有限差分离散，用半隐式二阶时间积分器求解。结果显示突触丢失时神经元的恢复能力。当受影响的突触发生钙泄漏时，神经元失去了产生突触到核钙信号的能力，这是学习、可塑性和神经元存活所必需的。下调钙结合蛋白浓度可部分恢复通往细胞核的信号通路。这些结果可以确定未来的研究途径，以稳定阿尔茨海默病期间的钙信号通路。利用MATLAB https://github.com/NeuroBox3D/CalcSim实现并求解了耦合电-钙模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

SIAM Journal on Applied Mathematics 数学-应用数学

CiteScore

3.60

自引率

0.00%

发文量

审稿时长

12 months

期刊介绍： SIAM Journal on Applied Mathematics (SIAP) is an interdisciplinary journal containing research articles that treat scientific problems using methods that are of mathematical interest. Appropriate subject areas include the physical, engineering, financial, and life sciences. Examples are problems in fluid mechanics, including reaction-diffusion problems, sedimentation, combustion, and transport theory; solid mechanics; elasticity; electromagnetic theory and optics; materials science; mathematical biology, including population dynamics, biomechanics, and physiology; linear and nonlinear wave propagation, including scattering theory and wave propagation in random media; inverse problems; nonlinear dynamics; and stochastic processes, including queueing theory. Mathematical techniques of interest include asymptotic methods, bifurcation theory, dynamical systems theory, complex network theory, computational methods, and probabilistic and statistical methods.