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An integrative dynamic model of brain energy metabolism using in vivo neurochemical measurements
Cloutier, Mathieu; Bolger, Fiachra B.; Lowry, John P.; Wellstead, Peter
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.
Keyword(s): Chemistry; Astrocytes; Brain energy metabolism; Kinetic modelling; Neurons; Systems biology.
Publication Date:
2009
Type: Journal article
Peer-Reviewed: Yes
Institution: Maynooth University
Citation(s): Cloutier, Mathieu and Bolger, Fiachra B. and Lowry, John P. and Wellstead, Peter (2009) An integrative dynamic model of brain energy metabolism using in vivo neurochemical measurements. Journal of Computational Neuroscience. ISSN 0929-5313
Publisher(s): Springer Science+Business Media
File Format(s): application/pdf
Related Link(s): https://mural.maynoothuniversity.ie/1664/1/PubVerfulltextcloutier.pdf
First Indexed: 2020-01-31 06:02:38 Last Updated: 2021-07-31 08:57:08