Abstract
In this paper, we combined several mathematical models of cerebral metabolism and nutrient transport to investigate the energetic significance of metabolite trafficking within the brain parenchyma during a 360-secs activation. Glycolytic and oxidative cellular metabolism were homogeneously modeled between neurons and astrocytes, and the stimulation-induced neuronal versus astrocytic Na inflow was set to 3:1. These assumptions resemble physiologic conditions and are supported by current literature. Simulations showed that glucose diffusion to the interstitium through basal lamina dominates the provision of the sugar to both neurons and astrocytes, whereas astrocytic endfeet transfer less than 4% of the total glucose supplied to the tissue. Neuronal access to paracellularly diffused glucose prevails even after halving (doubling) the ratio of neuronal versus astrocytic glycolytic (oxidative) metabolism, as well as after reducing the neuronal versus astrocytic Na+ inflow to a nonphysiologic value of 1:1. Noticeably, displaced glucose equivalents as intercellularly shuttled lactate account for ∼ 6% to 7% of total brain glucose uptake, an amount comparable with the concomitant drainage of the monocarboxylate by the bloodstream. Overall, our results suggest that the control of carbon recruitment for neurons and astrocytes is exerted at the level of glucose uptake rather than that of lactate shuttle.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 586-602 |
| Number of pages | 17 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 30 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2010 |
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Keywords
- Brain activation
- Energy metabolism
- Mathematical modeling
Cite this
Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics : Evidence from mathematical modeling. / Dinuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 30, No. 3, 01.03.2010, p. 586-602.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics
T2 - Evidence from mathematical modeling
AU - Dinuzzo, Mauro
AU - Mangia, Silvia
AU - Maraviglia, Bruno
AU - Giove, Federico
PY - 2010/3/1
Y1 - 2010/3/1
N2 - In this paper, we combined several mathematical models of cerebral metabolism and nutrient transport to investigate the energetic significance of metabolite trafficking within the brain parenchyma during a 360-secs activation. Glycolytic and oxidative cellular metabolism were homogeneously modeled between neurons and astrocytes, and the stimulation-induced neuronal versus astrocytic Na inflow was set to 3:1. These assumptions resemble physiologic conditions and are supported by current literature. Simulations showed that glucose diffusion to the interstitium through basal lamina dominates the provision of the sugar to both neurons and astrocytes, whereas astrocytic endfeet transfer less than 4% of the total glucose supplied to the tissue. Neuronal access to paracellularly diffused glucose prevails even after halving (doubling) the ratio of neuronal versus astrocytic glycolytic (oxidative) metabolism, as well as after reducing the neuronal versus astrocytic Na+ inflow to a nonphysiologic value of 1:1. Noticeably, displaced glucose equivalents as intercellularly shuttled lactate account for ∼ 6% to 7% of total brain glucose uptake, an amount comparable with the concomitant drainage of the monocarboxylate by the bloodstream. Overall, our results suggest that the control of carbon recruitment for neurons and astrocytes is exerted at the level of glucose uptake rather than that of lactate shuttle.
AB - In this paper, we combined several mathematical models of cerebral metabolism and nutrient transport to investigate the energetic significance of metabolite trafficking within the brain parenchyma during a 360-secs activation. Glycolytic and oxidative cellular metabolism were homogeneously modeled between neurons and astrocytes, and the stimulation-induced neuronal versus astrocytic Na inflow was set to 3:1. These assumptions resemble physiologic conditions and are supported by current literature. Simulations showed that glucose diffusion to the interstitium through basal lamina dominates the provision of the sugar to both neurons and astrocytes, whereas astrocytic endfeet transfer less than 4% of the total glucose supplied to the tissue. Neuronal access to paracellularly diffused glucose prevails even after halving (doubling) the ratio of neuronal versus astrocytic glycolytic (oxidative) metabolism, as well as after reducing the neuronal versus astrocytic Na+ inflow to a nonphysiologic value of 1:1. Noticeably, displaced glucose equivalents as intercellularly shuttled lactate account for ∼ 6% to 7% of total brain glucose uptake, an amount comparable with the concomitant drainage of the monocarboxylate by the bloodstream. Overall, our results suggest that the control of carbon recruitment for neurons and astrocytes is exerted at the level of glucose uptake rather than that of lactate shuttle.
KW - Brain activation
KW - Energy metabolism
KW - Mathematical modeling
UR - http://www.scopus.com/inward/record.url?scp=77649273782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77649273782&partnerID=8YFLogxK
U2 - 10.1038/jcbfm.2009.232
DO - 10.1038/jcbfm.2009.232
M3 - Article
C2 - 19888285
AN - SCOPUS:77649273782
VL - 30
SP - 586
EP - 602
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 3
ER -