scholarly journals Shifted Dynamics of Glucose Metabolism in the Hippocampus During Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Ivan Ge ◽  
Gregory Wohl Kirschen ◽  
Xinxing Wang

Aging is a process that adversely affects brain functions such as cognition. Brain activity is highly energy consuming, with glucose serving as the main energy source under normal circumstances. Whether the dynamics of glucose metabolism change with aging is not well understood. This study sought to investigate the activity-dependent changes in glucose metabolism of the mouse hippocampus during aging. In brief, after 1 h of contextual exploration in an enriched environmental condition or 1 h in a familiar home cage condition, metabolites were measured from the hippocampus of both young adult and aged mice with metabolomic profiling. Compared to the home cage context, the enriched contextual exploration condition resulted in changes in the concentration of 11 glucose metabolism-related metabolites in the young adult hippocampus. In contrast, glucose metabolism-related metabolite changes were more apparent in the aged group altered by contextual exploration when compared to those in the home cage condition. Importantly, in the aged groups, several key metabolites involved in glycolysis, the TCA cycle, and ketone body metabolism accumulated, suggesting the less efficient metabolization of glucose-based energy resources. Altogether, the analyses revealed that in the aged mice altered by enriched contextual exploration, the glucose resource seems to be unable to provide enough energy for hippocampal function.

2021 ◽  
Author(s):  
Ivan Ge ◽  
Gregory Kirschen ◽  
Xinxing Wang

Aging is a process that adversely affects brain functions such as cognitive behaviors. Brain activity is a high-energy consumption process. Glucose serves as the main energy source under normal circumstances. Whether the dynamics of glucose metabolism during aging remains unchanged is not well understood. This study sought to investigate the activity-dependent changes in glucose metabolism of the mouse hippocampus during aging. In brief, after one hour of contextual exploration in an enriched environmental condition or one hour in a familiar home cage condition, metabolites were measured from the hippocampus of both adult and aged mice with metabolomic profiling. Compared to the home cage context, the enriched contextual exploration condition resulted in changes in the concentration of 11 glucose metabolism-related metabolites in the adult hippocampus. In contrast, glucose metabolism-related metabolite changes were more apparent in the aged group during contextual exploration when compared to those in the home cage condition. Importantly, in the aged groups, several key metabolites involved in glycolysis, the TCA cycle, and ketone body metabolism accumulated, suggesting the less efficient metabolization of glucose-based energy resources. Altogether, the analyses revealed that in the aged mice during enriched contextual exploration, the glucose resource seems to be unable to provide enough energy for hippocampal function.


2018 ◽  
Vol 39 (9) ◽  
pp. 1710-1724 ◽  
Author(s):  
Tesfaye W Tefera ◽  
Karin Borges

Although alterations in energy metabolism are known in ALS, the specific mechanisms leading to energy deficit are not understood. We measured metabolite levels derived from injected [1-13C]glucose and [1,2-13C]acetate (i.p.) in cerebral cortex and spinal cord extracts of wild type and hSOD1G93A mice at onset and mid disease stages using high-pressure liquid chromatography, 1H and 13C nuclear magnetic resonance spectroscopy. Levels of spinal and cortical CNS total lactate, [3-13C]lactate, total alanine and [3-13C]alanine, but not cortical glucose and [1-13C]glucose, were reduced mostly at mid stage indicating impaired glycolysis. The [1-13C]glucose-derived [4-13C]glutamate, [4-13C]glutamine and [2-13C]GABA amounts were diminished at mid stage in cortex and both time points in spinal cord, suggesting decreased [3-13C]pyruvate entry into the TCA cycle. Lack of changes in [1,2-13C]acetate-derived [4,5-13C]glutamate, [4,5-13C]glutamine and [1,2-13C]GABA levels indicate unchanged astrocytic 13C-acetate metabolism. Reduced levels of leucine, isoleucine and valine in CNS suggest compensatory breakdown to refill TCA cycle intermediate levels. Unlabelled, [2-13C] and [4-13C]GABA concentrations were decreased in spinal cord indicating that impaired glucose metabolism contributes to hyperexcitability and supporting the use of treatments which increase GABA amounts. In conclusion, CNS glucose metabolism is compromised, while astrocytic TCA cycling appears to be normal in the hSOD1G93A mouse model at symptomatic disease stages.


2018 ◽  
Vol 299 ◽  
pp. 76-85 ◽  
Author(s):  
Wentao Li ◽  
Wenpeng Zhang ◽  
Mengyang Chang ◽  
Juan Ren ◽  
Wenping Xie ◽  
...  

2008 ◽  
Vol 20 (1) ◽  
pp. 149 ◽  
Author(s):  
R. G. Sturmey ◽  
H. J. Leese

Glucose metabolism plays an important role in the preimplantation development of porcine embryos in vitro. As in mammalian species generally, a proportion of glucose consumed is converted to lactate by aerobic glycolysis generating small amounts of ATP, with the remainder oxidized by the TCA cycle. However, a striking feature of the porcine early embryo is the large amount of lipid present as triglyceride (TG), which represents an alternative energy source. The TG is metabolized via β-oxidation, producing acetyl Co A, which in turn is oxidized by the TCA cycle. This sequence of reactions requires a constant supply of carbohydrate to provide oxaloacetate (OA) to prime the TCA cycle. The provision of OA from pyruvate arising from glycolysis may represent an alternative role for glucose in early pig embryo development. We have therefore sought to determine the importance of interplay between glucose and TG metabolism in porcine embryos in vitro. Porcine embryos were generated in vitro by fertilization of in vitro-matured oocytes collected from abattoir-derived ovaries. Oocytes were matured in defined maturation medium and embryos cultured in NCSU23. Glucose consumption, lactate production, and TG content of single porcine blastocysts cultured throughout development in the presence of methyl palmoxirate (MP), an inhibitor of TG metabolism, were measured as described by Sturmey RG and Leese HJ 2003 (Reprod. 126, 197–204). The capacity of zygotes to form blastocysts when cultured with OA in place of glucose in the presence or absence of MP and the amount of TG in blastocysts grown in either glucose or OA-containing medium were then determined (6 replicates). When TG metabolism was inhibited, porcine blastocysts consumed significantly more glucose (32 � 9 pmol/embryo/h v. 11 � 1 pmol/embryo/h; P < 0.05; n = 34) and produced higher amounts of lactate (35 � 4 pmol/embryo/h v. 10 � 0.8 pmol/embryo/h; P < 0.01; n = 34). Blastocyst rates did not differ significantly between embryos grown in the presence of glucose or OA, and in blastocysts grown in OA-NCSU the TG content was significantly reduced (155 � 8 ng v. 240 � 12 ng; P = 0.015; n = 41). All embryos cultured in OA-containing medium in the presence of MP failed to develop beyond the zygote stage. The data support the notion that porcine embryos can use endogenous TG as a metabolic energy source. When this is prevented by chemical inhibition, the embryo upregulates glycolysis and glucose oxidation as an alternate means of generating ATP. When cultured in medium containing OA, a compound that cannot generate ATP per se, embryo development was similar to controls, again suggesting the ability to use endogenous energy stores, a proposition reinforced by a significant fall in the levels of TG in the presence of OA. However, by inhibiting β-oxidation in the absence of glucose, porcine embryos were unable to develop. The relationship between TG and glucose metabolism by porcine embryos is analogous to the glucose/fatty acid cycle in whole animals where glucose and TG can be used as energy sources, but in a reciprocal manner. The data also demonstrate the plasticity of energy metabolism by porcine early embryos.


1986 ◽  
Vol 251 (5) ◽  
pp. C803-C809 ◽  
Author(s):  
R. T. Mallet ◽  
M. J. Jackson ◽  
J. K. Kelleher

The objective of this study was to characterize the effects of replacement of extracellular Na+ with a nontransportable cation, N-methyl-D-glucamine (NMDG+) on jejunal epithelial glucose metabolism. Jejunal epithelium isolated from male Sprague-Dawley rats was incubated in media containing 5 mM glucose, 0.5 mM glutamine, 0.5 mM beta-hydroxybutyrate, and 0.3 mM acetoacetate as the principal carbon sources. O2 consumption and total glucose utilization were reduced 30 and 50%, respectively, when Na+ was replaced with NMDG+. In both media, approximately 75% of utilized glucose carbon was converted to lactate. The rate of glucose metabolism via the hexose monophosphate shunt, as evaluated using specific 14CO2 yields from [1-14C]glucose and [6-14C]glucose, was not appreciably altered by Na+ replacement. Tricarboxylic acid (TCA) cycle flux was evaluated using 14CO2 production from [14C]glucose and [14C]pyruvate radioisotopes. Approximately 50% of TCA cycle flux was shunted into products other than CO2 in both media. The majority of the acetyl-CoA oxidized in the TCA cycle was derived from cytosolic pyruvate. It is concluded that removal of Na+ from the bathing medium substantially reduced glucose utilization via the Embden-Meyerhof pathway and TCA cycle in the jejunal epithelium.


2020 ◽  
Author(s):  
Riccardo Mobili ◽  
Sonia La Cognata ◽  
Francesca Merlo ◽  
Andrea Speltini ◽  
Massimo Boiocchi ◽  
...  

<div> <p>The extraction of the succinate dianion from a neutral aqueous solution into dichloromethane is obtained using a lipophilic cage-like dicopper(II) complex as the extractant. The quantitative extraction exploits the high affinity of the succinate anion for the cavity of the azacryptate. The anion is effectively transferred from the aqueous phase, buffered at pH 7 with HEPES, into dichloromethane. A 1:1 extractant:anion adduct is obtained. Extraction can be easily monitored by following changes in the UV-visible spectrum of the dicopper complex in dichloromethane, and by measuring the residual concentration of succinate in the aqueous phase by HPLC−UV. Considering i) the relevance of polycarboxylates in biochemistry, as e.g. normal intermediates of the TCA cycle, ii) the relevance of dicarboxylates in the environmental field, as e.g. waste products of industrial processes, and iii) the recently discovered role of succinate and other dicarboxylates in pathophysiological processes including cancer, our results open new perspectives for research in all contexts where selective recognition, trapping and extraction of polycarboxylates is required. </p> </div>


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