effects of transmitters and amyloid-beta peptide on calcium signals in rat cortical astrocytes fura-2am measurements and stochastic model simulations发射器和β-淀粉样蛋白肽在大鼠大脑皮质星形胶质细胞钙信号fura-2am测量和随机模型模拟.pdfVIP

Effects of Transmitters and Amyloid-Beta Peptide on Calcium Signals in Rat Cortical Astrocytes: Fura-2AM Measurements and Stochastic Model Simulations 1 1 2 3 1 Eeva Toivari *, Tiina Manninen , Amit K. Nahata , Tuula O. Jalonen , Marja-Leena Linne * 1 Department of Signal Processing, Tampere University of Technology, Tampere, Finland, 2 Kidney Care Center at DCI, Steubenville, Ohio, United States of America, 3 Department of Physiology and Neuroscience, School of Medicine, St. George’s University, Grenada, West Indies Abstract Background: To better understand the complex molecular level interactions seen in the pathogenesis of Alzheimer’s disease, the results of the wet-lab and clinical studies can be complemented by mathematical models. Astrocytes are known to become reactive in Alzheimer’s disease and their ionic equilibrium can be disturbed by interaction of the released and accumulated transmitters, such as serotonin, and peptides, including amyloid-b peptides (Ab). We have here studied the effects of small amounts of Ab25–35 fragments on the transmitter-induced calcium signals in astrocytes by Fura-2AM fluorescence measurements and running simulations of the detected calcium signals. Methodology/Principal Findings: Intracellular calcium signals were measured in cultured rat cortical astrocytes following additions of serotonin and glutamate, or either of these transmitters together with Ab25–35. Ab25–35 increased the number of astrocytes responding to glutamate and exceedingly increased the magnitude of the serotonin-induced calcium signals. In addition to Ab25–35-induced effects, the contribution of intracellular calcium stores to calcium signaling was tested. When using highe