Event Abstract

Computational model for astroglial cell function in Alzheimer's disease

  • 1 Tampere University of Technology, Finland
  • 2 Kidney Care Center at DCI, United States
  • 3 University of Jyväskylä, Finland

Neuritic plaques, consisting mostly of aggregated amyloid-β peptide, are some of the pathological findings in brains of Alzheimer's disease patients. The aggregated amyloid-β disturbs the cellular homeostasis, which can be monitored by e.g. measuring changes in the intracellular Ca2+ concentrations [Ca2+]. As an intracellular second messenger, Ca2+ functions as a mediator in transporting extracellular signals into the cell. Normally, the Ca2+ concentration in the cytosol is kept very low, but when signaling pathways are activated, oscillations of elevated Ca2+ levels can be measured. The aim of this study is to reproduce with a computational model the experimental data of the amyloid-β and serotonin induced Ca2+ oscillations in astrocytes.

To measure the effects of amyloid-β peptide aggregates and serotonin on Ca2+ oscillations, primary cortical astrocyte cultures were prepared from newborn Sprague-Dawley rat brain by growing the isolated astrocytes on coverslips in culture dishes in an incubator (37°C, 5 % CO2) for 1 - 4 weeks. Cells were then exposed to both amyloid-β peptide and serotonin. Ca2+ oscillation measurements were done using 4 μM fura-2 acetoxymethyl ester (Fura-2AM) and a monochromator-based spectrophotofluorimetric system (model RF D-4010 Deltascan; PTI, South Brunswick, NJ, U.S.A.) with dual excitation at the 340 and 380 nm wavelengths, bandpass of 2 nm, and the fluorescence emission measurements at 510 nm wavelength.

The aim of this study is to reproduce the experimental data with a computational model. Ca2+ oscillations in astrocytes can be modeled by deterministic differential equations as Lavrentovich and Hemkin have recently done in (J. Theor. Biol. 251(4), 553 - 560, 2008). In their model, three processes affecting the cytosolic [Ca2+] have been described; namely the flux of Ca2+ from/to ECM (extracellular matrix) and ER (endoplasmic reticulum), and the two feedback loops releasing Ca2+ via inositol (1,4,5)-trisphosphate receptors. In this work however, Ca2+ oscillations in astrocytes are modeled using stochastic differential equations to describe the experimentally measured Ca2+ oscillations.

In the Figure, there are stochastic Ca2+ oscillations obtained with the computational model designed for simulation of astroglial Ca2+ changes. The model makes it possible to study pathological phenomena associated with Alzheimer's disease. In particular, the model may help to clarify the basic mechanisms of Alzheimer's disease by modeling the effects of amyloid-β peptide aggregations on the important transmitter-induced intracellular Ca2+ fluctuations.

Conference: Neuroinformatics 2008, Stockholm, Sweden, 7 Sep - 9 Sep, 2008.

Presentation Type: Poster Presentation

Topic: Computational Neuroscience

Citation: Mäkiraatikka E, Manninen T, Nahata AK, Jalonen TO and Linne M (2008). Computational model for astroglial cell function in Alzheimer's disease. Front. Neuroinform. Conference Abstract: Neuroinformatics 2008. doi: 10.3389/conf.neuro.11.2008.01.049

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Received: 28 Jul 2008; Published Online: 28 Jul 2008.

* Correspondence: Eeva Mäkiraatikka, Tampere University of Technology, Tampere, Finland, eeva.makiraatikka@tut.fi

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