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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 Ī³-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

Performance of Morris water maze test in db/db (nā€‰=ā€‰7) and WT mice (nā€‰=ā€‰7). a Swim track; (b) Escape latency; (c) Time spent in goal area; (d) Number of crossing the original platform. Significant level: *Pā€‰<ā€‰0.05, **Pā€‰<ā€‰0.01, ***Pā€‰<ā€‰0.001
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Fig1: Performance of Morris water maze test in db/db (nā€‰=ā€‰7) and WT mice (nā€‰=ā€‰7). a Swim track; (b) Escape latency; (c) Time spent in goal area; (d) Number of crossing the original platform. Significant level: *Pā€‰<ā€‰0.05, **Pā€‰<ā€‰0.01, ***Pā€‰<ā€‰0.001

Mentions: The Morris water maze (MWM) test showed that escape latency of db/db mice was significantly longer than that of age-matched wild type (WT, Fig.Ā 1a and b) mice. In addition, db/db mice had a significantly shorter swimming time and crossing number as compared with the age-matched WT mice in the target quadrant during the probe trial in the MWM test (Fig.Ā 1c and d). Thus, results of the test indicate learning and memory deficits in db/db mice at 17-wk of age.Fig. 1


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)

Performance of Morris water maze test in db/db (nā€‰=ā€‰7) and WT mice (nā€‰=ā€‰7). a Swim track; (b) Escape latency; (c) Time spent in goal area; (d) Number of crossing the original platform. Significant level: *Pā€‰<ā€‰0.05, **Pā€‰<ā€‰0.01, ***Pā€‰<ā€‰0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Performance of Morris water maze test in db/db (nā€‰=ā€‰7) and WT mice (nā€‰=ā€‰7). a Swim track; (b) Escape latency; (c) Time spent in goal area; (d) Number of crossing the original platform. Significant level: *Pā€‰<ā€‰0.05, **Pā€‰<ā€‰0.01, ***Pā€‰<ā€‰0.001
Mentions: The Morris water maze (MWM) test showed that escape latency of db/db mice was significantly longer than that of age-matched wild type (WT, Fig.Ā 1a and b) mice. In addition, db/db mice had a significantly shorter swimming time and crossing number as compared with the age-matched WT mice in the target quadrant during the probe trial in the MWM test (Fig.Ā 1c and d). Thus, results of the test indicate learning and memory deficits in db/db mice at 17-wk of age.Fig. 1

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 Ī³-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