Baicalin reverses the impairment of synaptogenesis induced by dopamine burden via the stimulation of GABA(A)R-TrkB interaction in minimal hepatic encephalopathy

It has been reported that D1 receptor (D1R) activation reduces GABA(A) receptor (GABA(A)R) current, and baicalin (BAI) displays therapeutic efficacy in diseases involving cognitive impairment. We investigated the mechanisms by which BAI could improve DA-induced minimal hepatic encephalopathy (MHE) using immunoblotting, immunofluorescence, and co-immunoprecipitation. BAI did not induce toxicity on the primary cultured neurons. And no obvious toxicity of BAI to the brain was found in rats. DA activated D1R/dopamine and adenosine 3'5'-monophosphate-regulated phospho-protein (DARPP32) to reduce the GABA(A)R current; BAI treatment did not change the D1R/DARPP32 levels but blocked DA-induced reduction of GABA(A)R levels in primary cultured neurons. DA decreased the interaction of GABA(A)R with TrkB and the expression of downstream AKT, which was blocked by BAI treatment. Moreover, BAI reversed the decrease in the expression of GABA(A)R/TrkB/AKT and prevented the impairment of synaptogenesis and memory deficits in MHE rats. These results suggest that BAI has neuroprotective and synaptoprotective effects on MHE which are not related to upstream D1R/DARPP32 signaling, but to the targeting of downstream GABA(A)R signaling to TrkB.