Computational model of interacting system dynamics of calcium, IP3 and β-amyloid in ischemic neuron cells

Abstract

The study of single independent dynamics of calcium ([Ca2+]), IP3, and β-amyloid (Aβ) in neurons provide limited information. Some attempts are reported for the dynamics of two interacting systems of [Ca2+] and IP3, and calcium and Aβ, which gave some novel insights about the phenomena. However, the interactions of these three systems have not been analyzed till date in neurons. Therefore, a novel model is constructed to study the interactions of the spatiotemporal systems of [Ca2+], IP3, and Aβ in neurons. A two-way feedback mechanism between [Ca2+] and IP3, and [Ca2+] and Aβ has been incorporated into the model. The model is formulated by coupling three reaction-diffusion equations of [Ca2+], IP3 and Aβ, respectively. This coupling automatically takes care of the indirect two-way feedback process between IP3 and β-amyloid in neuron cells. The finite element method (FEM) with the Crank-Nicolson scheme (CNS) is utilized to study the contribution of various ER-associated processes like RyR, IP3R, SERCA pump, buffer approximation, etc on the neuronal interactions of [Ca2+], IP3, and β-amyloid during Ischemia. The numerical findings provide novel insights into alterations in ER handling during Ischemia, resulting in disturbances in the neuronal calcium, IP3, and Aβ levels, which may cause the advancement of Alzheimer’s illness and be responsible for neurotoxicity and cell death.