Simulation of Ca2+ oscillations in astrocytes mediated by amyloid beta in Alzheimer's disease

Disruptions of astrocyte Ca2+ signaling is important in Alzheimers disease (AD) with the unclear mechanism of amyloid beta peptide (A{beta}). We have modified our previous computational model of spontaneous Ca2+ oscillations in astrocytes to investigate the effects of A{beta} on intracellular Ca2+ dynamics. The simulation results have shown consistence with the previous experiments. A{beta} can increase the resting concentration of intracellular Ca2+ and change the regime of Ca2+ oscillations by activating L-type voltage-gated calcium channels and the metabolic glutamate receptors, or by increasing ryanodine receptors sensitivity and Ca2+ leakage, respectively. This work have provided a toolkit to study the influence of A{beta} on intracellular Ca2+ dynamics in AD. It is helpful for understanding the toxic role of A{beta} during the progression of AD. Statement of SignificanceAlzheimers disease (AD) is the most common neurodegenerative disease with the unclear mechanism of amyloid beta peptide (A{beta}). This work have implemented a computational model to address the Ca2+ dynamics of astrocyte mediated by A{beta} with the four different pathways: voltage-gated calcium channels, metabotropic glutamate receptors 5, ryanodine receptor channels and membrane leak. The Ca2+ oscillations and bifurcation diagram indicate that astrocytes exhibit ionic excitability mediated by A{beta} and become the potential targets of A{beta} neurotoxicity. We expect this shared computational model would advance the understanding of AD.