Baicalin reverses the impairment of synaptogenesis induced by dopamine burden via the stimulation of GABAR-TrkB interaction in minimal hepatic encephalopathy.

BACKGROUND

It has been reported that D1 receptor (DR) activation reduces GABA receptor (GABAR) current, and baicalin (BAI) displays therapeutic efficacy in diseases involving cognitive impairment.

METHODS

We investigated the mechanisms by which BAI could improve DA-induced minimal hepatic encephalopathy (MHE) using immunoblotting, immunofluorescence, and co-immunoprecipitation.

RESULTS

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 DR/dopamine and adenosine 3'5'-monophosphate-regulated phospho-protein (DARPP32) to reduce the GABAR current; BAI treatment did not change the DR/DARPP32 levels but blocked DA-induced reduction of GABAR levels in primary cultured neurons. DA decreased the interaction of GABAR with TrkB and the expression of downstream AKT, which was blocked by BAI treatment. Moreover, BAI reversed the decrease in the expression of GABAR/TrkB/AKT and prevented the impairment of synaptogenesis and memory deficits in MHE rats.

CONCLUSIONS

These results suggest that BAI has neuroprotective and synaptoprotective effects on MHE which are not related to upstream DR/DARPP32 signaling, but to the targeting of downstream GABAR signaling to TrkB.