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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

Pathological changes in hippocampus of db/db and WT mice. Apoptosis was examined by the TUNEL assay ((a), WT mice; (b), db/db mice with cognitive decline). Astrogliosis was evaluated by the GFAP method ((d), WT mice; (e), db/db mice). The numbers of TUNEL and GFAP-positive cells were counted blindly, as shown in (c and F), and an average was taken from five different fields of hippocampus in each group of mice (n = 4, Scale bars = 100 μm.). Significant level: **P < 0.01
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Fig2: Pathological changes in hippocampus of db/db and WT mice. Apoptosis was examined by the TUNEL assay ((a), WT mice; (b), db/db mice with cognitive decline). Astrogliosis was evaluated by the GFAP method ((d), WT mice; (e), db/db mice). The numbers of TUNEL and GFAP-positive cells were counted blindly, as shown in (c and F), and an average was taken from five different fields of hippocampus in each group of mice (n = 4, Scale bars = 100 μm.). Significant level: **P < 0.01

Mentions: Figure 2 illustrates the histological changes in hippocampus based on TUNEL assay and GFAP immunohistochemistry. It can be seen that number of TUNEL-positive cells were significantly increased in hippocampus of db/db mice with DACD compared to WT mice (Fig. 2a-c, P < 0.01), which suggests that there was more neuronal apoptosis in hippocampus of db/db mice. Moreover, relative to WT mice, the expression of GFAP, which is a key indicator of astrocyte reactivity, was increased significantly in db/db mice with DACD (Fig. 2d–f, P < 0.01).Fig. 2


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)

Pathological changes in hippocampus of db/db and WT mice. Apoptosis was examined by the TUNEL assay ((a), WT mice; (b), db/db mice with cognitive decline). Astrogliosis was evaluated by the GFAP method ((d), WT mice; (e), db/db mice). The numbers of TUNEL and GFAP-positive cells were counted blindly, as shown in (c and F), and an average was taken from five different fields of hippocampus in each group of mice (n = 4, Scale bars = 100 μm.). Significant level: **P < 0.01
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Pathological changes in hippocampus of db/db and WT mice. Apoptosis was examined by the TUNEL assay ((a), WT mice; (b), db/db mice with cognitive decline). Astrogliosis was evaluated by the GFAP method ((d), WT mice; (e), db/db mice). The numbers of TUNEL and GFAP-positive cells were counted blindly, as shown in (c and F), and an average was taken from five different fields of hippocampus in each group of mice (n = 4, Scale bars = 100 μm.). Significant level: **P < 0.01
Mentions: Figure 2 illustrates the histological changes in hippocampus based on TUNEL assay and GFAP immunohistochemistry. It can be seen that number of TUNEL-positive cells were significantly increased in hippocampus of db/db mice with DACD compared to WT mice (Fig. 2a-c, P < 0.01), which suggests that there was more neuronal apoptosis in hippocampus of db/db mice. Moreover, relative to WT mice, the expression of GFAP, which is a key indicator of astrocyte reactivity, was increased significantly in db/db mice with DACD (Fig. 2d–f, P < 0.01).Fig. 2

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