Analysis of Angiotensin Metabolism in the Kidney Using Mass Spectrometry.
Analysis of Angiotensin Metabolism in the Kidney Using Mass Spectrometry.
复制标题
使用质谱法分析肾脏中的血管紧张素代谢。
DOI：
10.1007/978-1-4939-7030-8_15
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Elased,KhalidM
中科院分区：
文献类型：
--
作者：
Grobe,Nadja;Elased,KhalidM
认知和情绪障碍是2型糖尿病常见的中枢神经系统并发症，尽管其神经机制尚不清楚。以往的研究主要集中在神经元输入，如突触可塑性的改变。轴突初始段（Axon initial segment， AIS）是神经元内调节神经元输出的特殊功能区域。AIS的结构变化被认为是各种精神和神经疾病的关键病理生理事件。在这里，我们评估了db/dbmice大脑AIS的结构完整性，db/dbmice是一种与认知和情绪障碍相关的2型糖尿病动物模型。我们在2型糖尿病发生前（5周龄）和发生后（10周龄）以及糖尿病患者每日运动治疗后评估AIS。我们发现，通过AIS结构蛋白βIV谱蛋白的免疫染色，2型糖尿病的发展与内侧前额叶皮层和海马的AIS显著缩短有关。AIS缩短发生在神经元和AIS蛋白水平没有改变的情况下。我们发现Ranvier节点没有变化，Ranvier是另一个与AIS共享类似分子组织的神经元功能域。这是第一个确定2型糖尿病患者AIS改变的研究。由于已知AIS缩短会降低神经元的兴奋性，我们的研究结果可能为理解和治疗2型糖尿病的认知和情绪障碍提供新的途径。
Cognitive and mood impairments are common central nervous system complications of type 2 diabetes, although the neuronal mechanism(s) remains elusive. Previous studies focused mainly on neuronal inputs such as altered synaptic plasticity. Axon initial segment (AIS) is a specialized functional domain within neurons that regulates neuronal outputs. Structural changes of AIS have been implicated as a key pathophysiological event in various psychiatric and neurological disorders. Here we evaluated the structural integrity of the AIS in brains ofdb/dbmice, an established animal model of type 2 diabetes associated with cognitive and mood impairments. We assessed the AIS before (5 weeks of age) and after (10 weeks) the development of type 2 diabetes, and after daily exercise treatment of diabetic condition. We found that the development of type 2 diabetes is associated with significant AIS shortening in both medial prefrontal cortex and hippocampus, as evident by immunostaining of the AIS structural protein βIV spectrin. AIS shortening occurs in the absence of altered neuronal and AIS protein levels. We found no change in nodes of Ranvier, another neuronal functional domain sharing a molecular organization similar to the AIS. This is the first study to identify AIS alteration in type 2 diabetes condition. Since AIS shortening is known to lower neuronal excitability, our results may provide a new avenue for understanding and treating cognitive and mood impairments in type 2 diabetes.
使用 HPLC-电喷雾串联质谱法测量血浆肾素活性。
影响因子：
9.3
作者：
V. Fredline;E. Kovács;P. Taylor;A. G. Johnson
通讯作者：
A. G. Johnson
人肾小球内皮细胞对血管紧张素肽的酶促加工。
DOI：
10.1152/ajprenal.00087.2012
发表时间：
2012
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Velez,JuanCarlosQ;Ierardi,JessalynL;Bland,AlisonM;Morinelli,ThomasA;Arthur,JohnM;Raymond,JohnR;Janech,MichaelG
通讯作者：
Janech,MichaelG