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Aubert2005 - Interaction between astrocytes and neurons on energy metabolism

ABSTRACT: Aubert2005 - Interaction between astrocytes and neurons on energy metabolism Enocded non-curated model. Issues: - Confusing equations A.41 and A.42 - Missing values for parameters Vv,0 and dHb,0 This model is described in the article: Interaction between astrocytes and neurons studied using a mathematical model of compartmentalized energy metabolism. Aubert A, Costalat R. J. Cereb. Blood Flow Metab. 2005 Nov; 25(11): 1476-1490 Abstract: Understanding cerebral energy metabolism in neurons and astrocytes is necessary for the interpretation of functional brain imaging data. It has been suggested that astrocytes can provide lactate as an energy fuel to neurons, a process referred to as astrocyte-neuron lactate shuttle (ANLS). Some authors challenged this hypothesis, defending the classical view that glucose is the major energy substrate of neurons, at rest as well as in response to a stimulation. To test the ANLS hypothesis from a theoretical point of view, we developed a mathematical model of compartmentalized energy metabolism between neurons and astrocytes, adopting hypotheses highly unfavorable to ANLS. Simulation results can be divided between two groups, depending on the relative neuron versus astrocyte stimulation. If this ratio is low, ANLS is observed during all the stimulus and poststimulus periods (continuous ANLS), but a high ratio induces ANLS only at the beginning of the stimulus and during the poststimulus period (triphasic behavior). Finally, our results show that current experimental data on lactate kinetics are compatible with the ANLS hypothesis, and that it is essential to assess the neuronal and astrocytic NADH/NAD+ ratio changes to test the ANLS hypothesis. This model is hosted on BioModels Database and identified by: MODEL1411210000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Audald Lloret i Villas

PROVIDER: MODEL1411210000 | BioModels | 2015-02-25

REPOSITORIES: BioModels

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Interaction between astrocytes and neurons studied using a mathematical model of compartmentalized energy metabolism.

Aubert Agnès A Costalat Robert R

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20051101 11

Understanding cerebral energy metabolism in neurons and astrocytes is necessary for the interpretation of functional brain imaging data. It has been suggested that astrocytes can provide lactate as an energy fuel to neurons, a process referred to as astrocyte-neuron lactate shuttle (ANLS). Some authors challenged this hypothesis, defending the classical view that glucose is the major energy substrate of neurons, at rest as well as in response to a stimulation. To test the ANLS hypothesis from a ...[more]

PMID: 15931164

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Project description:In order to obtain a global view of energy metabolism pathways of the sulfate-reducer Desulfovibrio vulgaris Hildenborough and the proteins involved therein whole-genome microarrays were used to compare the transcriptional response of cells grown with hydrogen/sulfate, pyruvate/sulfate, lactate/thiosulfate, and pyruvate with limiting sulfate, relative to growth in standard lactate/sulfate condition. Growth with hydrogen/sulfate showed the largest number of differently expressed genes and the largest changes in expression levels. The most up-regulated energy metabolism genes were those coding for the periplasmic [NiFeSe] hydrogenase, followed by the Ech hydrogenase, and the most down-regulated were genes coding for the Coo hydrogenase. The results point to the involvement of formate cycling and the ethanol pathway during growth on hydrogen, whereas there is evidence for CO cycling during growth on lactate and pyruvate, but not on H2. Growth with thiosulfate showed the hallmarks of a reduced energy status of the cells with down regulation of the ATP synthase and the Qmo and Dsr complexes., whereas growth with pyruvate showed the smallest differences but an increased role for the Ech hydrogenase.that in this case functions in reverse from the case of growth with H2. The multiple periplasmic hydrogenases and formate dehydrogenases, do not display the same regulation pattern showing that their metabolic roles are not totally interchangeable. This result together with the observation that several genes coding for proteins that have not been biochemically characterised were considerably affected in this study, reveals a more complex energy metabolism than previously considered and provides guidance for further studies. Keywords: Growth protocol Desulfovibrio vulgaris from our laboratory culture collection was cultured at 37°C with pyruvate as the only substrate (without sulfate as the electron acceptor) to mid-log phase. Cultures were also cultivated similarly in Lactate-Sulfate medium to mid-log phase. Gene expression profiles of cultures grown under pyruvate fermentation were compared with those of the cultures grown via sulfate reduction. Total RNA was harvested from four replicate cultures for microarray analysis. RNA extraction, purification, and labeling were performed independently on each cell sample.Two samples of each total RNA preparation were labeled, one with Cy3-dUTP and another with Cy5-dUTP for microarray hybridization.

Project description:In order to obtain a global view of energy metabolism pathways of the sulfate-reducer Desulfovibrio vulgaris Hildenborough and the proteins involved therein whole-genome microarrays were used to compare the transcriptional response of cells grown with hydrogen/sulfate, pyruvate/sulfate, lactate/thiosulfate, and pyruvate with limiting sulfate, relative to growth in standard lactate/sulfate condition. Growth with hydrogen/sulfate showed the largest number of differently expressed genes and the largest changes in expression levels. The most up-regulated energy metabolism genes were those coding for the periplasmic [NiFeSe] hydrogenase, followed by the Ech hydrogenase, and the most down-regulated were genes coding for the Coo hydrogenase. The results point to the involvement of formate cycling and the ethanol pathway during growth on hydrogen, whereas there is evidence for CO cycling during growth on lactate and pyruvate, but not on H2. Growth with thiosulfate showed the hallmarks of a reduced energy status of the cells with down regulation of the ATP synthase and the Qmo and Dsr complexes., whereas growth with pyruvate showed the smallest differences but an increased role for the Ech hydrogenase.that in this case functions in reverse from the case of growth with H2. The multiple periplasmic hydrogenases and formate dehydrogenases, do not display the same regulation pattern showing that their metabolic roles are not totally interchangeable. This result together with the observation that several genes coding for proteins that have not been biochemically characterised were considerably affected in this study, reveals a more complex energy metabolism than previously considered and provides guidance for further studies. Keywords: Growth protocol Desulfovibrio vulgaris Hildenborough was cultured at 37°C with pyruvate as the only electron donor (with sulfate as the electron acceptor) to mid-log phase. Cultures were also cultivated similarly using lactate as the sole electron donor to mid-log phase. Gene expression profiles of cultures grown with pyruvate as the electron donor were compared with those of the cultures grown with lactate as the electron donor for sulfate reduction. Total RNA was harvested from three replicate cultures for microarray analysis. RNA extraction, purification, and labeling were performed independently on each cell sample.Two samples of each total RNA preparation were labeled, one with Cy3-dUTP and another with Cy5-dUTP for microarray hybridization (dye swap).

Project description:In order to obtain a global view of energy metabolism pathways of the sulfate-reducer Desulfovibrio vulgaris Hildenborough and the proteins involved therein whole-genome microarrays were used to compare the transcriptional response of cells grown with hydrogen/sulfate, pyruvate/sulfate, lactate/thiosulfate, and pyruvate with limiting sulfate, relative to growth in standard lactate/sulfate condition. Growth with hydrogen/sulfate showed the largest number of differently expressed genes and the largest changes in expression levels. The most up-regulated energy metabolism genes were those coding for the periplasmic [NiFeSe] hydrogenase, followed by the Ech hydrogenase, and the most down-regulated were genes coding for the Coo hydrogenase. The results point to the involvement of formate cycling and the ethanol pathway during growth on hydrogen, whereas there is evidence for CO cycling during growth on lactate and pyruvate, but not on H2. Growth with thiosulfate showed the hallmarks of a reduced energy status of the cells with down regulation of the ATP synthase and the Qmo and Dsr complexes., whereas growth with pyruvate showed the smallest differences but an increased role for the Ech hydrogenase.that in this case functions in reverse from the case of growth with H2. The multiple periplasmic hydrogenases and formate dehydrogenases, do not display the same regulation pattern showing that their metabolic roles are not totally interchangeable. This result together with the observation that several genes coding for proteins that have not been biochemically characterised were considerably affected in this study, reveals a more complex energy metabolism than previously considered and provides guidance for further studies. Keywords: Growth protocol Desulfovibrio vulgaris from our laboratory culture collection was cultured at 37°C with hydrogen as the only electron donor (with sulfate as the electron acceptor) to mid-log phase. Cultures were also cultivated similarly using lactate as the sole electron donor to mid-log phase. Gene expression profiles of cultures grown with hydrogen as the electron donor were compared with those of the cultures grown with lactate as the electron donor for sulfate reduction. Total RNA was harvested from four replicate cultures for microarray analysis. RNA extraction, purification, and labeling were performed independently on each cell sample.Two samples of each total RNA preparation were labeled, one with Cy3-dUTP and another with Cy5-dUTP for microarray hybridization (dye swap).

Project description:In order to obtain a global view of energy metabolism pathways of the sulfate-reducer Desulfovibrio vulgaris Hildenborough and the proteins involved therein whole-genome microarrays were used to compare the transcriptional response of cells grown with hydrogen/sulfate, pyruvate/sulfate, lactate/thiosulfate, and pyruvate with limiting sulfate, relative to growth in standard lactate/sulfate condition. Growth with hydrogen/sulfate showed the largest number of differently expressed genes and the largest changes in expression levels. The most up-regulated energy metabolism genes were those coding for the periplasmic [NiFeSe] hydrogenase, followed by the Ech hydrogenase, and the most down-regulated were genes coding for the Coo hydrogenase. The results point to the involvement of formate cycling and the ethanol pathway during growth on hydrogen, whereas there is evidence for CO cycling during growth on lactate and pyruvate, but not on H2. Growth with thiosulfate showed the hallmarks of a reduced energy status of the cells with down regulation of the ATP synthase and the Qmo and Dsr complexes., whereas growth with pyruvate showed the smallest differences but an increased role for the Ech hydrogenase.that in this case functions in reverse from the case of growth with H2. The multiple periplasmic hydrogenases and formate dehydrogenases, do not display the same regulation pattern showing that their metabolic roles are not totally interchangeable. This result together with the observation that several genes coding for proteins that have not been biochemically characterised were considerably affected in this study, reveals a more complex energy metabolism than previously considered and provides guidance for further studies. Keywords: Growth protocol Desulfovibrio vulgaris Hildenborough was cultured at 37°C with thiosulfate as the only electron acceptor (with lactate as the electron donor) to mid-log phase. Cultures were also cultivated similarly using sulfate as the sole electron acceptor to mid-log phase. Gene expression profiles of cultures grown with thiosulfate as the electron acceptor were compared with those of the cultures grown with sulfate as the electron acceptor for dissimilatory sulfate reductiontion. Total RNA was harvested from four replicate cultures for microarray analysis. RNA extraction, purification, and labeling were performed independently on each cell sample. Two samples of each total RNA preparation were labeled, one with Cy3-dUTP and another with Cy5-dUTP for microarray hybridization (dye swap).

Dataset Information

Aubert2005 - Interaction between astrocytes and neurons on energy metabolism

Publications

Interaction between astrocytes and neurons studied using a mathematical model of compartmentalized energy metabolism.

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