Overview

Neurons need energy in order to function, and if denied energy they will start to selectively shut down less essential functions and eventually die. A possible contributory factor to PD development would be a deficit in either the acquisition and/or effective use of energy by neurons. Neurons require much more energy than other body cells, as the brain accounts for 2% of the body weight but uses up to 20% of the energy substrates. Thus, neurons may be more prone to failures associated with cellular inefficiencies. In addition, there is evidence that the neurons most affected are those with the highest energy requirements - these are usually neurons with extended axons and/or lightly myelinated axons.

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Research

Brain metabolism involves multiple interacting mechanisms and two cellular species (astrocytes and neurons) that produce energy from substrates such as oxygen and glucose to maintain cerebral function (see figure). The systems biology approach allows assessing these interactions both at the experimental and theoretical levels. At the experimental level, in vivo measurements using biosensors allows measuring the dynamic response of energy metabolism in the cerebral tissue (see the Sensor Technology for Neurochemical Applications website for further details). Using this data and available models for brain energy metabolism (see the works from Aubert, Costalat and co-workers), it is possible to build an integrative modelling of energy trafficking in the cerebral tissue. We believe that a better understanding of brain energy metabolism through mathematical description of underlying biological processes will improve our understanding of energetic failures as a root cause in PD development. Since energy is used or produced in all cellular mechanisms, a physiological model for energy metabolism can be used as the ‘backbone’ to build a model database of mechanisms involved in PD development. Globally, the SoPD project will aim at the inclusion of major phenomenon that could be linked to energy metabolism and PD. These include, but are not limited to:

• Energy production from energy substrates and biothermodynamics of the brain.
• Energy expenditure for cellular maintenance (α-synuclein disposal).
• Brain energy metabolism under ‘imbalanced’ conditions (perturbation, oxidative stress, disease etc.).
• Implications of cellular aging on energy metabolism.
• Control and systems theory in energy metabolism.

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Contact point

• Prof. Peter Wellstead.
• Prof. John Lowry.

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Selected References

Bolger, F.B., Serra, P.A., Dalton, M., O’Neill, R.D., Fillenz, M. and Lowry, J.P. Real-time monitoring of brain extracellular lactate. In Monitoring Molecules in Neuroscience, pp. 286-288, 2006. Di Chiara, G., Carboni, E., Valentini, V., Acquas, E., Bassareo, V. and Cadoni, C. (Eds.) University of Cagliari Press, Cagliara, Italy.

Lowry, J.P. and O'Neill, R.D. Neuroanalytical Chemistry In Vivo Using Biosensors. In Encyclopedia of Sensors, pp. 501-524, 2005. Grimes CA and Dickey EC (Eds.), American Scientific Publishers, CA, American Scientific Publishers, CA, ISBN: 1-58883-062-4.

Aubert A, Costalat R. A Model of the Coupling between Brain Electrical Activity, Metabolism, and Hemodynamics: Application to the Interpretation of Functional Neuroimaging. NeuroImage, 17:1162-1181, 2002.

Aubert A, Costalat R. Interactions between astrocytes and neurons studied using a mathematical of compartimentalized energy metabolism. Journal of Cerebral Blood Flow and Metabolism, 25:1476-1490, 2005.

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