Cloutier, Mathieu and Bolger, Fiachra B. and Lowry, John P. and Wellstead, Peter
An integrative dynamic model of brain energy metabolism
using in vivo neurochemical measurements.
Journal of Computational Neuroscience.
An integrative, systems approach to the modelling
of brain energy metabolism is presented. Mechanisms
such as glutamate cycling between neurons and astrocytes
and glycogen storage in astrocytes have been implemented.
A unique feature of the model is its calibration using in vivo
data of brain glucose and lactate from freely moving rats
under various stimuli. The model has been used to perform
simulated perturbation experiments that show that glycogen
breakdown in astrocytes is significantly activated during
sensory (tail pinch) stimulation. This mechanism provides
an additional input of energy substrate during high
consumption phases. By way of validation, data from the
perfusion of 50μM propranolol in the rat brain was
compared with the model outputs. Propranolol affects the
glucose dynamics during stimulation, and this was accurately
reproduced in the model by a reduction in the glycogen breakdown in astrocytes. The model’s predictive
capacity was verified by using data from a sensory
stimulation (restraint) that was not used for model calibration. Finally, a sensitivity analysis was conducted on the model parameters, this showed that the control of energy metabolism and transport processes are critical in the
metabolic behaviour of cerebral tissue.
||Astrocytes; Brain energy metabolism;
Kinetic modelling; Neurons; Systems biology.
||Faculty of Science and Engineering > Chemistry
||16 Nov 2009 15:51
|Journal or Publication Title:
||Journal of Computational Neuroscience
||Springer Science+Business Media
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