Hydrogen Sulfide Attenuates the Cognitive Dysfunction in Parkinson's Disease Rats via Promoting Hippocampal Microglia M2 Polarization by Enhancement of Hippocampal Warburg Effect

Identification of innovative therapeutic targets for the treatment of cognitive impairment in Parkinson's disease (PD) is urgently needed. Hydrogen sulfide (H(2)S) plays an important role in cognitive function. Therefore, this work is aimed at investigating whether H(2)S attenuates the cognitive impairment in PD and the underlying mechanisms. In the rotenone- (ROT-) established PD rat model, NaHS (a donor of H(2)S) attenuated the cognitive impairment and promoted microglia polarization from M1 towards M2 in the hippocampus of PD rats. NaHS also dramatically upregulated the Warburg effect in the hippocampus of PD rats. 2-Deoxyglucose (2-DG, an inhibitor of the Warburg effect) abolished NaHS-upregulated Warburg effect in the hippocampus of PD rats. Moreover, the inhibited hippocampal Warburg effect by 2-DG abrogated H(2)S-excited the enhancement of hippocampal microglia M2 polarization and the improvement of cognitive function in ROT-exposed rats. Our data demonstrated that H(2)S inhibits the cognitive dysfunction in PD via promoting microglia M2 polarization by enhancement of hippocampal Warburg effect.