Metabonomic profiles delineate potential role of glutamate-glutamine cycle in db/db mice with diabetes-associated cognitive decline.
Metabonomic profiles delineate potential role of glutamate-glutamine cycle in db/db mice with diabetes-associated cognitive decline.
复制标题
代谢组学特征描述了谷氨酸-谷氨酰胺循环在糖尿病相关认知能力下降的 db/db 小鼠中的潜在作用
DOI：
10.1186/s13041-016-0223-5
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发表时间：
2016-04-18
期刊：
影响因子：
3.6
通讯作者：
Gao H
中科院分区：
文献类型：
--
作者：
Zheng Y;Yang Y;Dong B;Zheng H;Lin X;Du Y;Li X;Zhao L;Gao H
背景：糖尿病相关认知功能减退是糖尿病的中枢神经系统并发症之一，其发病机制尚不清楚。本研究采用（1）H核磁共振代谢组学和免疫组化方法，对认知功能减退的db/db小鼠海马关键代谢改变进行了研究，以期进一步了解认知功能减退的发病机制。认知功能下降的db/db小鼠海马中琥珀酸和柠檬酸等三羧酸循环中间产物减少。此外，在db/db小鼠中观察到谷氨酰胺水平升高以及谷氨酸和γ-氨基丁酸水平降低。免疫组织化学分析结果表明，谷氨酰胺合成酶增加，转氨酶和谷氨酸脱羧酶下降db/db mice.Conclusions：我们的研究结果表明，糖尿病相关的认知功能下降db/db小鼠的发展是最有可能牵连的能量代谢减少和谷氨酸-谷氨酰胺穿梭神经元和星形胶质细胞之间的海马障碍。
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.