The Neurotrophic and Anti-Inflammatory Effect of β-asarone on the DA-Induced the Pathology of Minimal Hepatic Encephalopathy

Abstract

Background: The mechanism underlying the impaired cognitive function and memory loss in Minimal hepatic encephalopathy (MHE) remains unclear. Dopamine (DA) is reported to be associated with dementia. Methods: In this study, we investigated mechanism underlying DA-induced MHE pathology by immunoblotting, ELISA, FM4-64 and fluorescence staining. Results: We observed that MHE brains showed the increased content of DA, after administration of anti-DA antibody, and cognitive loss in MHE rats was recovered to the normal level, indicating the involvement of DA in the pathogenesis of MHE. Moreover, DA (10 μM) treatment obviously induced the decrease in the production of GDNF/NGF and the increase in TNFα levels in primary cultured neurons, which were blocked by addition of β-asarone (βASA). We also demonstrated that DA stimulated the activation of ASK1/JNK1 pathway. and the addition of anti-TNFα antibody reversed the inactivation of Notch signaling, the downregulation of neurotrophins and synaptic loss.Conclusions: Overall, we suggested that DA stimulated abundant production and secretion of neuronal TNFα, which elicited progressive loss of neurotrophic factors, leading to cognitive disorder of MHE.