Authors: Saidan Ding Weikan Wang Xuebao Wang Yong Liang Leping Liu Yiru Ye Jianjing Yang Hongchang Gao Qichuan Zhuge
Publish Date: 2015/10/03
Volume: 53, Issue: 8, Pages: 5324-5343
Abstract
Dopamine DAinduced learning and memory impairment is well documented in minimal hepatic encephalopathy MHE but the contribution of DA to neurodegeneration and the involved underlying mechanisms are not fully understood In this study the effect of DA on neuronal apoptosis was initially detected The results showed that MHE/DA 10 μgtreated rats displayed neuronal apoptosis However we found that DA 10 μM treatment did not induce evident apoptosis in primary cultured neurons PCNs but did produce TNFα in primary cultured astrocytes PCAs Furthermore cocultures between PCAs and PCNs exposed to DA exhibited increased astrocytic TNFα levels and neuronal apoptosis compared with cocultures exposed to the vehicle indicating the attribution of the neuronal apoptosis to astrocytic TNFα We also demonstrated that DA enhanced TNFα production from astrocytes by activation of the TLR4/MyD88/NFκB pathway and secreted astrocytic TNFαpotentiated neuronal apoptosis through inactivation of the PI3K/Akt/mTOR pathway Overall the findings from this study suggest that DA stimulates substantial production and secretion of astrocytic TNFα consequently and indirectly triggering progressive neurodegeneration resulting in cognitive decline and memory loss in MHE
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