Diabetic db/db mice exhibit central nervous system and peripheral molecular alterations as seen in neurological disorders.

Diabetic db/db mice exhibit central nervous system and peripheral molecular alterations as seen in neurological disorders.
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DOI:
10.1038/tp.2013.42
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发表时间:
2013-05-28
影响因子:
6.8
通讯作者:
Bahn S
Bahn S
中科院分区:
医学1区
文献类型:
--
作者:
Ernst A;Sharma AN;Elased KM;Guest PC;Rahmoune H;Bahn S

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db/db小鼠是糖尿病研究中广泛使用的临床前模型。最近的研究表明,这些老鼠也表现出精神病和类似抑郁症的行为,就像在一些精神疾病中看到的那样。在这里,我们对来自db/db和对照小鼠的血浆和脑样本进行了多重免疫分析和液相色谱质谱分析,以确定可能与这些行为异常相关的改变通路。这是首次在该模型中对大脑蛋白质组进行分析的研究。与对照组小鼠相比,db/db小鼠的血浆中瘦素和胰岛素水平升高,YY肽、胰高血糖素和催乳素水平降低,炎症相关蛋白发生改变。来自db/db小鼠的额叶皮层组织显示出与能量代谢、细胞结构和神经功能有关的蛋白质的变化,海马体中涉及相同途径的蛋白质发生了变化,并对细胞信号蛋白产生了额外的影响。这些发现与2型糖尿病、精神分裂症、重度抑郁症和阿尔茨海默病的影响重叠,可能有助于代谢和神经疾病中常见的内表型。
The db/db mouse is a widely used preclinical model in diabetes research. Recent studies have shown that these mice also display aspects of psychosis and depression-like behaviors as seen in some psychiatric disorders. Here, we have performed multiplex immunoassay and liquid chromatography mass spectrometry profiling of the plasma and brain samples from db/db and control mice to identify altered pathways, which could be related to these behavioral abnormalities. This is the first study to carry out profiling of the brain proteome in this model. Plasma from the db/db mice had increased levels of leptin and insulin, decreased levels of peptide YY, glucagon and prolactin and alterations in inflammation-related proteins, compared with control mice. Frontal cortex tissue from the db/db mice showed changes in proteins involved in energy metabolism, cellular structure and neural functioning, and the hippocampus had changes in proteins involved in the same pathways, with additional effects on cellular signalling proteins. The overlap of these findings with effects seen in type 2 diabetes, schizophrenia, major depressive disorder and Alzheimer's disease might contribute to a common endophenotype seen in metabolic and neurological disorders.
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