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Metabonomic profiles delineate potential role of glutamate-glutamine cycle in db/db mice with diabetes-associated cognitive decline.

Zheng Y, Yang Y, Dong B, Zheng H, Lin X, Du Y, Li X, Zhao L, Gao H - Mol Brain (2016)

Bottom Line: Diabetes-associated cognition decline is one of central nervous system complications in diabetic mellitus, while its pathogenic mechanism remains unclear.Moreover, an increase in glutamine level and a decrease in glutamate and γ-aminobutyric acid levels were observed in db/db mice.Our results suggest that the development of diabetes-associated cognition decline in db/db mice is most likely implicated in a reduction in energy metabolism and a disturbance of glutamate-glutamine shuttling between neurons and astrocytes in hippocampus.

View Article: PubMed Central - PubMed

Affiliation: Radiology Department of the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.

ABSTRACT

Background: Diabetes-associated cognition decline is one of central nervous system complications in diabetic mellitus, while its pathogenic mechanism remains unclear. In this study, (1)H nuclear magnetic resonance-based metabonomics and immunohistochemistry was used to explore key metabolic alterations in hippocampus of type 2 diabetic db/db mice with cognition decline in order to advance understanding of mechanisms underlying the pathogenesis of the disease.

Results: Metabonomics reveals that lactate level was significantly increased in hippocampus of db/db mice with cognition decline compared with age-matched wild-type mice. Several tricarboxylic acid cycle intermediates including succinate and citrate were reduced in hippocampus of db/db mice with cognition decline. Moreover, an increase in glutamine level and a decrease in glutamate and γ-aminobutyric acid levels were observed in db/db mice. Results from immunohistochemistry analysis show that glutamine synthetase was increased and glutaminase and glutamate decarboxylase were decreased in db/db mice.

Conclusions: Our results suggest that the development of diabetes-associated cognition decline in db/db mice is most likely implicated in a reduction in energy metabolism and a disturbance of glutamate-glutamine shuttling between neurons and astrocytes in hippocampus.

No MeSH data available.


Related in: MedlinePlus

Changes in metabolite levels in the hippocampus of db/db mice with cognitive decline (red circle, n = 7) and WT mice (■, n = 11) obtained from NMR-based metabonomics. Significant level: *P < 0.05, **p < 0.01
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Fig5: Changes in metabolite levels in the hippocampus of db/db mice with cognitive decline (red circle, n = 7) and WT mice (■, n = 11) obtained from NMR-based metabonomics. Significant level: *P < 0.05, **p < 0.01

Mentions: To further confirm the metabolic changes, the levels of the metabolites were quantified and analyzed by t-test as shown in Fig. 5 and Additional file 1: Table S1. NAA level, a marker for neuronal viability, was decreased significantly in db/db mice with DACD (9.79 ± 0.37 vs 10.46 ± 0.22, p < 0.001). Lactate content in hippocampus of db/db mice with DACD was significantly increased (27.36 ± 2.89 vs 19.97 ± 0.60, p < 0.001). In addition, several tricarboxylic acid (TCA)-cycle-related metabolites, such as pyruvate, succinate and citrate, were also found significantly reduced in db/db mice with DACD. Taurine is a sulfur-containing amino acid that plays important roles on regulating osmolality of the astrocytes. In the present study, a significantly elevated level of taurine was observed in db/db mice with DACD (18.20 ± 0.83 vs 16.84 ± 0.45, p < 0.001).Fig. 5


Metabonomic profiles delineate potential role of glutamate-glutamine cycle in db/db mice with diabetes-associated cognitive decline.

Zheng Y, Yang Y, Dong B, Zheng H, Lin X, Du Y, Li X, Zhao L, Gao H - Mol Brain (2016)

Changes in metabolite levels in the hippocampus of db/db mice with cognitive decline (red circle, n = 7) and WT mice (■, n = 11) obtained from NMR-based metabonomics. Significant level: *P < 0.05, **p < 0.01
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835835&req=5

Fig5: Changes in metabolite levels in the hippocampus of db/db mice with cognitive decline (red circle, n = 7) and WT mice (■, n = 11) obtained from NMR-based metabonomics. Significant level: *P < 0.05, **p < 0.01
Mentions: To further confirm the metabolic changes, the levels of the metabolites were quantified and analyzed by t-test as shown in Fig. 5 and Additional file 1: Table S1. NAA level, a marker for neuronal viability, was decreased significantly in db/db mice with DACD (9.79 ± 0.37 vs 10.46 ± 0.22, p < 0.001). Lactate content in hippocampus of db/db mice with DACD was significantly increased (27.36 ± 2.89 vs 19.97 ± 0.60, p < 0.001). In addition, several tricarboxylic acid (TCA)-cycle-related metabolites, such as pyruvate, succinate and citrate, were also found significantly reduced in db/db mice with DACD. Taurine is a sulfur-containing amino acid that plays important roles on regulating osmolality of the astrocytes. In the present study, a significantly elevated level of taurine was observed in db/db mice with DACD (18.20 ± 0.83 vs 16.84 ± 0.45, p < 0.001).Fig. 5

Bottom Line: Diabetes-associated cognition decline is one of central nervous system complications in diabetic mellitus, while its pathogenic mechanism remains unclear.Moreover, an increase in glutamine level and a decrease in glutamate and γ-aminobutyric acid levels were observed in db/db mice.Our results suggest that the development of diabetes-associated cognition decline in db/db mice is most likely implicated in a reduction in energy metabolism and a disturbance of glutamate-glutamine shuttling between neurons and astrocytes in hippocampus.

View Article: PubMed Central - PubMed

Affiliation: Radiology Department of the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.

ABSTRACT

Background: Diabetes-associated cognition decline is one of central nervous system complications in diabetic mellitus, while its pathogenic mechanism remains unclear. In this study, (1)H nuclear magnetic resonance-based metabonomics and immunohistochemistry was used to explore key metabolic alterations in hippocampus of type 2 diabetic db/db mice with cognition decline in order to advance understanding of mechanisms underlying the pathogenesis of the disease.

Results: Metabonomics reveals that lactate level was significantly increased in hippocampus of db/db mice with cognition decline compared with age-matched wild-type mice. Several tricarboxylic acid cycle intermediates including succinate and citrate were reduced in hippocampus of db/db mice with cognition decline. Moreover, an increase in glutamine level and a decrease in glutamate and γ-aminobutyric acid levels were observed in db/db mice. Results from immunohistochemistry analysis show that glutamine synthetase was increased and glutaminase and glutamate decarboxylase were decreased in db/db mice.

Conclusions: Our results suggest that the development of diabetes-associated cognition decline in db/db mice is most likely implicated in a reduction in energy metabolism and a disturbance of glutamate-glutamine shuttling between neurons and astrocytes in hippocampus.

No MeSH data available.


Related in: MedlinePlus