NeuronGlial: Mathematical Modeling of the Interplay between Neuron and Glial Cells
Project Topic
Mathematical Modeling of the Interplay between Neuron and Glial Cells
Project Description
Glial cells serve a variety of functions in nervous systems, some of
which are activated by neurotransmitters released from neurons. Glial
cells respond to these neurotransmitters via receptors, but also take up
some of the transmitters to help terminate the synaptic process. Among
these, glutamate uptake by glial cells is pivotal to avoid
transmitter-mediated excitotoxicity. In [4], a new model is proposed in
which glutamate uptake via the excitatory amino acid transporter (EAAT)
is functionally coupled to other glial transporters, in particular the
sodium-bicarbonate cotransporter (NBC) and the monocarboxylate
transporter (MCT), as well as other glial functions, such as calcium
signaling, a high potassium conductance and CO2 consumption. The central
issue of this hypothesis is that the shuttling of sodium ions and
acid/base equivalents, which drive the metabolite transport across the
glial membrane, cooperate with each other, and hence save energy. As a
result, glutamate removal from synaptic domains and lactate secretion
serving the energy supply to neurons would be facilitated and could
operate with greater capacity.
Even though the principle of the interplay between neuron and glial
cells seems to be relatively well understood, the above described model
is still a hypothesis. The importance of many involved elements, such as
the different transporters, the glutamate triggered calcium signaling,
the effect of extra- and intracellular carbonic anhydrase, remain
relatively unknown. In this work we will build a mathematical model of
the system, based on the above hypothesis, and validate it using
measurement data. The expected outcome of this work is a consistent
mathematical model of the interplay between neuron and glial cells,
which in turn will lead to a deeper biological understanding of this
system that might be crucial for certain types of diseases. The project
team consists of a mix of theoreticians and experimentalists, which is
crucial to be able to efficiently determine reaction and transport
kinetics and relevant parameters.
Project Members
Project Chair
Participating Research Groups
- Fraunhofer Institute for Industrial Mathematics (ITWM), Sect. System Analysis, Prognosis and Control (formerly Sect. Adaptive Systems)
Scientific Personnel
- Dr. Patrick Lang (Fraunhofer Institute for Industrial Mathematics (ITWM), Sect. System Analysis, Prognosis and Control (formerly Sect. Adaptive Systems))
- Christian Salzig (Fraunhofer Institute for Industrial Mathematics (ITWM), Sect. System Analysis, Prognosis and Control (formerly Sect. Adaptive Systems))
- Dr. Mats Jirstrand (Fraunhofer Chalmers Centre, Sect. Systems Biology and Bioinformatics)
- Dr. Henning Schmidt (Fraunhofer Chalmers Centre, Sect. Systems Biology and Bioinformatics)
- Joachim Almquist (Fraunhofer Chalmers Centre, Sect. Systems Biology and Bioinformatics)
- Prof. Dr. Joachim Deitmer (General Zoology Group, Department of Biology)
- Dr. Holger Becker (General Zoology Group, Department of Biology)
External Cooperation
- Fraunhofer Chalmers Centre, Sect. Systems Biology and Bioinformatics
- University of Kaiserslautern, Department of Biology, General Zoology Group
Project Events and Achievements
Project Time Frame
Project start: April 1, 2006
May 15-18, 2006: Internal Workshop
Initial consultation and presentation of existing competences and
software tools.
Data collection and first modelling approaches.
September 25-27, 2006: Internal Workshop with
Presentation of the devoloped models. Consultation for possible
model extension und further proceeding.
November 20-24:
Internal workshop. Modeling of protein-protein interaction and
enhancement of parameter estimation methods.
December 6-8:
Project meeting. Presentation of actual results, design of further
experiments and modeling approaches.
February - May, 2007:
Research visit of Joachim Almquist (Fraunhofer Chalmers Centre) in Kaiserslautern, joint activities with Sect. System Analysis, Prognosis and Control (formerly Sect. Adaptive Systems) and General Zoology Group.
February 28 - March 1, 2007:
Presentation of the project at the DASMOD Workshop.
March 21-24, 2007:
Poster presentation Modeling the Interplay between Neurons and Glial Cells by Joachim Almquist (Fraunhofer Chalmers Centre)
2nd Workshop on
Mathematical Aspects of Systems Biology
Göteborg, March 21-24, 2007 in Göteborg, Sweden.
April 18-20, 2007:
NeuronGlial project meeting in Kaiserslautern, for summarizing previous project activities and preparation of paper drafts (Sect. System Analysis, Prognosis and Control (formerly Sect. Adaptive Systems), Sect. Systems Biology and Bioinformatics, and General Zoology Group)
May 30 - June 1, 2007:
Poster presentation Modeling the Interplay between Neurons and Glial Cells (Joachim Almquist et al., presented by Christian Salzig, Sect. System Analysis, Prognosis and Control (formerly Sect. Adaptive Systems)) at
European BioPerspectives, Annual Convention of Biotechologists in Cologne, Germany.
Project Publications
Joachim Almquist, Holger Becker, Christian Salzig, Henning Schmidt. In:
European BioPerspectives, Annual Convention of Biotechologists, Book of Abstracts. P. 259, Poster Presentation, May, 2007
Joachim Almquist, Holger Becker, Christian Salzig, Henning Schmidt. In:
2nd Workshop on Mathematical Aspects of Systems Biology, Göteborg, Sweden, March 21-24, 2007. Poster Presentation, March, 2007
Henning Schmidt, Mats Jirstrand, Gunnar Cedersund. In:
7th International Conference On Systems Biology, Yokohama, Japan. October, 2006
