TY - JOUR
T1 - Glial-neuronal interactions underlying fructose utilization in rat hippocampal slices
AU - Izumi, Y.
AU - Zorumski, C. F.
N1 - Funding Information:
This work was supported in part by National Institutes of Health grants MH07791, AG18434 and AA12951, Alzheimer's Disease Research Center of Washington University and the Bantly Foundation.
PY - 2009/7/7
Y1 - 2009/7/7
N2 - Although fructose is commonly used as a sweetener, its effects on brain function are unclear. Using rat hippocampal slices, we found that fructose and mannose, like pyruvate, preserve ATP levels during 3-h of glucose deprivation. Similarly, fructose and mannose restored synaptic potentials (excitatory postsynaptic potential, EPSPs) depressed during glucose deprivation. However, restoration of synaptic responses was slow and only partial with fructose. EPSPs supported by mannose were inhibited by cytochalasin B (CCB), a glucose transport inhibitor, but were not inhibited by α-cyano-4-hydroxycinnamate (4-CIN), a monocarboxylate transport inhibitor, indicating that neurons use mannose via glucose transporters. In contrast, both CCB and 4-CIN depressed EPSPs supported by fructose, suggesting that fructose may be taken up by non-neuronal cells through CCB sensitive hexose transporters and metabolized to a monocarboxylate for subsequent use during neuronal respiration. Supporting this possibility, 20 minutes of oxygen deprivation in the presence of fructose resulted in functional and morphological deterioration whereas oxygen deprivation in the presence of glucose or mannose had minimal toxic effects. These results indicate that neuronal fructose utilization differs from glucose and mannose and likely involves release of monocarboxylates from glia.
AB - Although fructose is commonly used as a sweetener, its effects on brain function are unclear. Using rat hippocampal slices, we found that fructose and mannose, like pyruvate, preserve ATP levels during 3-h of glucose deprivation. Similarly, fructose and mannose restored synaptic potentials (excitatory postsynaptic potential, EPSPs) depressed during glucose deprivation. However, restoration of synaptic responses was slow and only partial with fructose. EPSPs supported by mannose were inhibited by cytochalasin B (CCB), a glucose transport inhibitor, but were not inhibited by α-cyano-4-hydroxycinnamate (4-CIN), a monocarboxylate transport inhibitor, indicating that neurons use mannose via glucose transporters. In contrast, both CCB and 4-CIN depressed EPSPs supported by fructose, suggesting that fructose may be taken up by non-neuronal cells through CCB sensitive hexose transporters and metabolized to a monocarboxylate for subsequent use during neuronal respiration. Supporting this possibility, 20 minutes of oxygen deprivation in the presence of fructose resulted in functional and morphological deterioration whereas oxygen deprivation in the presence of glucose or mannose had minimal toxic effects. These results indicate that neuronal fructose utilization differs from glucose and mannose and likely involves release of monocarboxylates from glia.
KW - ATP
KW - GLUT11
KW - GLUT8
KW - glycolysis
KW - hexose
KW - monocarboxylate
UR - http://www.scopus.com/inward/record.url?scp=67349161831&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2009.04.008
DO - 10.1016/j.neuroscience.2009.04.008
M3 - Article
C2 - 19362122
AN - SCOPUS:67349161831
VL - 161
SP - 847
EP - 854
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 3
ER -