CREB is upregulated in hepatic encephalopathy and contributes to the neuroprotection against neuroinflammation

Background: The cyclic adenosine monophosphate (cAMP) response element (CRE)-binding protein (CREB) is the key transcription factor in the brain which strengthens cell connection. This study was intended to determine whether CREB affect neurological decline in a hepatic encephalopathy animal model under trial conditions. Methods: Hepatic encephalopathy was induced in C57BL/6 mice via intraperitoneal injection of azoxymethane (AOM) in the presence or absence of 2-naphthol AS-E phosphate (KG-501). Mice were monitored for neurological decline and time to coma was recorded. The mice cortex were collected until coma and were used for real-time PCR and immunoblot analysis to assess the consequences on proinflammatory cytokine expression and the phosphorylation levels of the main factors in signaling pathway. Results: The expression of CREB was significantly elevated in AOM-treated mice cortex. But in KG-501 prior injection to AOM-treated mice cortex, the concentrations of chemokine (C-C motif) ligand 2 (CCL2) and CREB were significantly decreased. KG-501 significantly promoted the neurological outcomes of AOM-treated mice, reduced phosphorylation of ERK and the concentration of cAMP in cortex. Conclusions: These findings suggested that CREB was elevated following acute liver injury and CREB was involved in neurological decline associated with hepatic encephalopathy and the cAMP/ERK signaling pathway.