Differential Levels of Hippo Signaling in Selected Brain and Peripheral Tissues in Streptozotocin-Induced Cognitive Dysfunction in Mice.
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.
['Yu|Fan|F|', 'Han|Wei|W|', 'Zhan|Gaofeng|G|', 'Li|Shan|S|', 'Jiang|Xiaohong|X|', 'Xiang|Shoukui|S|', 'Zhu|Bin|B|', 'Yang|Ling|L|', 'Hua|Dongyu|D|', 'Luo|Ailin|A|', 'Hua|Fei|F|', 'Yang|Chun|C|']
D048868:Adaptor Proteins, Signal Transducing D000818:Animals D001921:Brain D018797:Cell Cycle Proteins D060825:Cognitive Dysfunction D003921:Diabetes Mellitus, Experimental D003922:Diabetes Mellitus, Type 1 D017228:Hepatocyte Growth Factor D007668:Kidney D008099:Liver D008297:Male D018782:Maze Learning D051379:Mice D008810:Mice, Inbred C57BL D023421:Models, Animal D017346:Protein Serine-Threonine Kinases D011518:Proto-Oncogene Proteins D015398:Signal Transduction D013311:Streptozocin D000091102:YAP-Signaling Proteins
Hippo signaling Cognitive dysfunction Diabetes Streptozotocin