IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0017914.html
   My bibliography  Save this article

Effects of Transmitters and Amyloid-Beta Peptide on Calcium Signals in Rat Cortical Astrocytes: Fura-2AM Measurements and Stochastic Model Simulations

Author

Listed:
  • Eeva Toivari
  • Tiina Manninen
  • Amit K Nahata
  • Tuula O Jalonen
  • Marja-Leena Linne

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- peptides (A). We have here studied the effects of small amounts of A25–35 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 A25–35. A25–35 increased the number of astrocytes responding to glutamate and exceedingly increased the magnitude of the serotonin-induced calcium signals. In addition to A25–35-induced effects, the contribution of intracellular calcium stores to calcium signaling was tested. When using higher stimulus frequency, the subsequent calcium peaks after the initial peak were of lower amplitude. This may indicate inadequate filling of the intracellular calcium stores between the stimuli. In order to reproduce the experimental findings, a stochastic computational model was introduced. The model takes into account the major mechanisms known to be involved in calcium signaling in astrocytes. Model simulations confirm the principal experimental findings and show the variability typical for experimental measurements. Conclusions/Significance: Nanomolar A25–35 alone does not cause persistent change in the basal level of calcium in astrocytes. However, even small amounts of A25–35, together with transmitters, can have substantial synergistic effects on intracellular calcium signals. Computational modeling further helps in understanding the mechanisms associated with intracellular calcium oscillations. Modeling the mechanisms is important, as astrocytes have an essential role in regulating the neuronal microenvironment of the central nervous system.

Suggested Citation

  • Eeva Toivari & Tiina Manninen & Amit K Nahata & Tuula O Jalonen & Marja-Leena Linne, 2011. "Effects of Transmitters and Amyloid-Beta Peptide on Calcium Signals in Rat Cortical Astrocytes: Fura-2AM Measurements and Stochastic Model Simulations," PLOS ONE, Public Library of Science, vol. 6(3), pages 1-9, March.
  • Handle: RePEc:plo:pone00:0017914
    DOI: 10.1371/journal.pone.0017914
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017914
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0017914&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0017914?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Mark P. Mattson, 2004. "Pathways towards and away from Alzheimer's disease," Nature, Nature, vol. 430(7000), pages 631-639, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ngoumen Ngassa Dany Joel & Ngondi Judith Laure & Oben Julius Enyong, 2021. "Effect of Autranella congolensis on Lipid Profile of Rats' Brain with Experimentally Induced Alzheimer's Disease," Journal of Food Research, Canadian Center of Science and Education, vol. 9(4), pages 1-60, December.
    2. Ying Shi & Alexander R. Pilozzi & Xudong Huang, 2020. "Exposure of CuO Nanoparticles Contributes to Cellular Apoptosis, Redox Stress, and Alzheimer’s A? Amyloidosis," IJERPH, MDPI, vol. 17(3), pages 1-18, February.
    3. Gema Lordén & Jacob M. Wozniak & Kim Doré & Lara E. Dozier & Chelsea Cates-Gatto & Gentry N. Patrick & David J. Gonzalez & Amanda J. Roberts & Rudolph E. Tanzi & Alexandra C. Newton, 2022. "Enhanced activity of Alzheimer disease-associated variant of protein kinase Cα drives cognitive decline in a mouse model," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Shu Jiang & Yijun Xie & Graham A. Colditz, 2021. "Functional ensemble survival tree: Dynamic prediction of Alzheimer’s disease progression accommodating multiple time‐varying covariates," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 70(1), pages 66-79, January.
    5. Seyed-Ali Sadegh-Zadeh & Chandrasekhar Kambhampati, 2018. "Computational Investigation of Amyloid Peptide Channels in Alzheimer’s Disease," J, MDPI, vol. 2(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0017914. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.