RETRACTED: DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy (Retracted Article)

被引:2
|
作者
Ding, Saidan [1 ]
Zhuge, Weishan [2 ]
Wang, Xuebao [3 ]
Yang, Jianjing [4 ]
Lin, Yuanshao [5 ]
Wang, Chengde [4 ]
Hu, Jiangnan [4 ]
Zhuge, Qichuan [4 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 1, Dept Surg Lab, Zhejiang Prov Key Lab Aging & Neurol Dis Res, Wenzhou, Peoples R China
[2] Wenzhou Med Univ, Affiliated Hosp 1, Gastrointestinal Surg, Wenzhou, Peoples R China
[3] Wenzhou Med Univ, Analyt & Testing Ctr, Wenzhou, Peoples R China
[4] Wenzhou Med Univ, Affiliated Hosp 1, Neurosurg Dept, Wenzhou, Peoples R China
[5] Wenzhou Med Univ, Affiliated Hosp 1, Neurol Dept, Wenzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
minimal hepatic encephalopathy; dopamine; insulin-like growth factor I; ERK1/2/RSK pathway; PSD95-nNOS interaction; GROWTH-FACTOR-I; NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; SIGNAL-TRANSDUCTION; ALZHEIMERS-DISEASE; PROTEIN-KINASE; MICE LACKING; INSULIN; DOPAMINE; RATS;
D O I
10.3389/fncel.2017.00258
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.
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页数:15
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