Hippocampal warburg effect mediates hydrogen sulfide-ameliorated diabetes-associated cognitive dysfunction: Involving promotion of hippocampal synaptic plasticity

Our previous studies have reported that hydrogen sulfide (H₂S) has ability to improve diabetes-associated cognitive dysfunction (DACD), but the exact mechanisms remain unknown. Recent research reveals that Warburg effect is associated with synaptic plasticity which plays a key role in cognition promotion. Herein, the present study was aimed to demonstrate whether hippocampal Warburg effect contributes to H₂S-ameliorated DACD and further explore its potential mechanism. We found that H₂S promoted the hippocampal Warburg effect and inhibited the OxPhos in the hippocampus of STZ-induced diabetic rats. It also improved the hippocampal synaptic plasticity in STZ-induced diabetic rats, as evidenced by the change of microstructures and the expression of different key-enzymes. Furthermore, inhibited hippocampal Warburg effect induced by DCA markedly abolished the improvement of H₂S on synaptic plasticity in the hippocampus of STZ-induced diabetic rats. DCA blocked H₂S-attenuated the cognitive dysfunction in STZ-induced diabetic rats, according to the Y-maze, Novel Objective Recognition, and Morris Water Maze tests. Collectively, these findings indicated that the hippocampal Warburg effect mediates H₂S-ameliorated DACD by improving hippocampal synaptic plasticity.