Differential Levels of Hippo Signaling in Selected Brain and Peripheral Tissues in Streptozotocin-Induced Cognitive Dysfunction in Mice
Differential Levels of Hippo Signaling in Selected Brain and Peripheral Tissues in Streptozotocin-Induced Cognitive Dysfunction in Mice
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链脲佐菌素引起的小鼠认知功能障碍中选定大脑和周围组织中 Hippo 信号传导的差异水平
DOI：
10.1016/j.neuroscience.2019.09.018
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发表时间：
2019-11
期刊：
影响因子：
3.3
通讯作者：
Yang Chun
中科院分区：
文献类型：
--
作者：
Yu Fan;Han Wei;Zhan Gaofeng;Li Shan;Jiang Xiaohong;Xiang Shoukui;Zhu Bin;Yang Ling;Hua Dongyu;Luo Ailin;Hua Fei;Yang Chun
越来越多的研究表明，代谢紊乱，特别是糖尿病，是阿尔茨海默病（AD）和其他神经退行性疾病的高危因素。据报道，糖尿病患者容易患有认知功能障碍（CD）。糖代谢异常和β淀粉样蛋白（Aβ）沉积与糖尿病CD的发生密切相关，但其确切机制尚不清楚。本研究采用链脲佐菌素连续5 d腹腔注射建立糖尿病小鼠模型，并根据Morris水迷宫实验（MWMT）结果，采用层次聚类分析法将糖尿病小鼠分为CD型和Non-CD型。此外，我们还检测了Hippo信号通路，包括哺乳动物不育20样蛋白激酶1（MST 1）、大肿瘤抑制蛋白1（LATS 1）、Yes相关蛋白（雅普）和雅普磷酸化（p-雅普）在脑和外周组织中的表达。与对照组小鼠相比，CD小鼠内侧前额叶皮层（mPFC）、纹状体和海马中MST 1、LATS 1和p-YAP/YAP比值均升高，而CD小鼠肠组织中MST 1、LATS 1和p-YAP/YAP比值降低。mPFC、前扣带皮层（anterior cingulate cortex，ACC）和海马中p-雅普/雅普比值与逃避潜伏期呈显著正相关，肝、肾和肠组织中LATS 1水平与逃避潜伏期呈显著正相关。总之，Hippo信号转导的改变可能有助于糖尿病诱导的CD。因此，改善Hippo信号传导的治疗干预可能有利于治疗糖尿病诱导的CD和其他神经退行性疾病。
Increasing studies have revealed that metabolic disorders, especially diabetes, are high risk factors for the development of Alzheimer’s disease (AD) and other neurodegenerative diseases. It has been reported that patients with diabetes are prone to suffer from cognitive dysfunction (CD). Although abnormal glucose metabolism and deposition of amyloid β (Aβ) are proven to have a closely relationship with diabetes-induced CD, its exact mechanism is still undetermined. In this study, a total of 14 mice were intraperitoneally injected with streptozotocin for 5 consecutive days to mimic diabetic models, and then hierarchical cluster analysis was adopted to classify the diabetic mice into CD and Non-CD phenotypes by the results of Morris water maze test (MWMT). Furthermore, we detected Hippo signaling including mammalian sterile 20-like protein kinases1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP) and phosphorylation of YAP (p-YAP) in brain and peripheral tissues. As compared with control mice, the levels of MST1, LATS1 and p-YAP/YAP ratio were increased in medial prefrontal cortex (mPFC), striatum and hippocampus of CD mice, while these proteins were decreased in gut tissue of CD mice. Additionally, there were significant positive correlations between escape latency and p-YAP/YAP ratio in mPFC, anterior cingulate cortex (ACC) and hippocampus, as well as the level of LATS1 in liver, kidney and gut tissues. In conclusion, alterations in Hippo signaling may contribute to CD induced by diabetes. Therefore, therapeutic interventions improving Hippo signaling might be beneficial to the treatment of diabetes-induced CD and other neurodegenerative diseases.
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DOI：
--
发表时间：
2010-07
期刊：
Brain and nerve = Shinkei kenkyu no shinpo
影响因子：
--
作者：
T. Tomiyama
通讯作者：
T. Tomiyama
影响因子：
7.2
作者：
Selkoe, Dennis J.
通讯作者：
Selkoe, Dennis J.
影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
影响因子：
5.3
作者：
Li D;Ni H;Rui Q;Gao R;Chen G
通讯作者：
Chen G
影响因子：
168.9
作者：
Ballard, Clive;Gauthier, Serge;Jones, Emma
通讯作者：
Jones, Emma