Statistical analysis of metabolic pathways of brain metabolism at steady state

R. Occhipinti, Michelle Puchowicz, J. C. Lamanna, E. Somersalo, D. Calvetti

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The estimation of metabolic fluxes for brain metabolism is important, among other things, to test the validity of different hypotheses which have been proposed in the literature. The metabolic model that we propose considers, in addition to the blood compartment, the cytosol, and mitochondria of both astrocyte and neuron, including detailed metabolic pathways. In this work we use a recently developed methodology to perform a statistical Flux Balance Analysis (FBA) for this model. The methodology recasts the problem in the form of Bayesian statistical inference and therefore can take advantage of qualitative information about brain metabolism for the simultaneous estimation of all reaction fluxes and transport rates at steady state. By a Markov Chain Monte Carlo (MCMC) sampling method, we are able to provide for each reaction flux and transport rate a distribution of possible values. The analysis of the histograms of the reaction fluxes and transport rates provides a very useful tool for assessing the validity of different hypotheses about brain energetics proposed in the literature, and facilitates the design of the pathways network that is in accordance with what is understood of the functioning of the brain. In this work, we focus on the analysis of biochemical pathways within each cell type (astrocyte and neuron) at different levels of neural activity, and we demonstrate how statistical tools can help implement various bounds suggested by experimental data.

Original languageEnglish (US)
Pages (from-to)886-902
Number of pages17
JournalAnnals of Biomedical Engineering
Volume35
Issue number6
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

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Metabolism
Brain
Statistical methods
Fluxes
Neurons
Mitochondria
Markov processes
Blood
Metabolic Networks and Pathways
Sampling
Astrocytes

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering

Cite this

Statistical analysis of metabolic pathways of brain metabolism at steady state. / Occhipinti, R.; Puchowicz, Michelle; Lamanna, J. C.; Somersalo, E.; Calvetti, D.

In: Annals of Biomedical Engineering, Vol. 35, No. 6, 01.06.2007, p. 886-902.

Research output: Contribution to journalArticle

Occhipinti, R. ; Puchowicz, Michelle ; Lamanna, J. C. ; Somersalo, E. ; Calvetti, D. / Statistical analysis of metabolic pathways of brain metabolism at steady state. In: Annals of Biomedical Engineering. 2007 ; Vol. 35, No. 6. pp. 886-902.
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