高血糖诱导老年雌性五岛-纪崎（GK）大鼠产生阿尔茨海默病相关蛋白，并促进突触蛋白丢失。
Hyperglycemia induced the Alzheimer's proteins and promoted loss of synaptic proteins in advanced-age female Goto-Kakizaki (GK) rats.
作者信息
Pintana Hiranya, Apaijai Nattayaporn, Kerdphoo Sasiwan, Pratchayasakul Wasana, Sripetchwandee Jirapas, Suntornsaratoon Panan, Charoenphandhu Narattaphol, Chattipakorn Nipon, Chattipakorn Siriporn C
机构信息
Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
出版信息
Neurosci Lett. 2017 Aug 10;655:41-45. doi: 10.1016/j.neulet.2017.06.041. Epub 2017 Jun 24.
Although both type 2 diabetes mellitus (T2DM) and aging are related with Alzheimer's disease (AD), the effects of aging on the Alzheimer's proteins and the synaptic markers in T2DM have not been investigated. This study, we hypothesized that T2DM rats with advanced-age, aggravates the reduction of synaptic proteins and an increase in the Alzheimer's protein markers. Goto-Kakizaki rats (GK) were used as a T2DM group and wild-type rats (WT) were used as a control group. Rats in each group were categorized by age into young-adult (7 months) and advanced-age rats (12.5 months). Blood was collected in all rats to determine plasma glucose and insulin levels. The brains were used for determining the level of Alzheimer's and synaptic proteins. Our data demonstrated that GK rats had a decreased body weight and increased blood glucose levels, compared to their age-matched WT. p-Tau was increased in both advanced-age WT and GK, compared to their young-adult rats. Moreover, amyloid-beta (Aβ) level was higher in advanced-age GK than their age-matched WT. The synaptic proteins were decreased in advanced-age GK, compared to young-adult GK rats. However, no difference in the level of Alzheimer's proteins and synaptic proteins in the brains of young-adult GK compared to age-matched WT was found. Our data suggested that aging contributes to the pathogenesis of AD and the reduction of synaptic proteins to greater extent in a diabetic than in a healthy condition.
尽管2型糖尿病（T2DM）和衰老都与阿尔茨海默病（AD）相关，但衰老对T2DM中阿尔茨海默病相关蛋白和突触标志物的影响尚未得到研究。在本研究中，我们假设高龄T2DM大鼠会加剧突触蛋白的减少和阿尔茨海默病蛋白标志物的增加。将Goto-Kakizaki大鼠（GK）作为T2DM组，野生型大鼠（WT）作为对照组。每组大鼠按年龄分为青年成年组（7个月）和高龄组（12.5个月）。采集所有大鼠的血液以测定血糖和胰岛素水平。取脑用于测定阿尔茨海默病相关蛋白和突触蛋白的水平。我们的数据表明，与年龄匹配的WT大鼠相比，GK大鼠体重降低，血糖水平升高。与青年成年大鼠相比，高龄WT和GK大鼠的磷酸化tau蛋白（p-Tau）均增加。此外，高龄GK大鼠的β淀粉样蛋白（Aβ）水平高于其年龄匹配的WT大鼠。与青年成年GK大鼠相比，高龄GK大鼠突触蛋白减少。然而，未发现青年成年GK大鼠脑内阿尔茨海默病相关蛋白和突触蛋白水平与年龄匹配的WT大鼠有差异。我们的数据表明，衰老在糖尿病状态下比健康状态下更能促进AD的发病机制和突触蛋白的减少。
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