Hydrogen sulfide attenuates depression-like behaviours in Parkinson's disease model rats by improving synaptic plasticity in a hippocampal Warburg effect-dependent manner.

ABSTRACT

BACKGROUND: Depression is a highly prevalent comorbidity arising in patients with Parkinson's disease (PD). However, depression in patients with PD is poorly treated. Hydrogen sulfide (H2S), a neuromodulator, has the potential to relieve depression. OBJECTIVE: To investigate whether H2S attenuates depression-like behaviours in a rat model of PD and examine the underlying mechanisms. METHODS: We utilised rotenone to develop a PD model with subcutaneous injections in the dorsal cervical region of Sprague-Dawley rats. The depression-like behaviours in the rotenone-induced PD model rats were assessed through forced swimming, tail suspension, open field, novelty-suppressed feeding, and elevated plus-maze tests. The expression of postsynaptic density protein-95 and synapsin-1, related to synaptic plasticity, was detected using Western blot in the hippocampus. The hippocampal ultrastructure, including the synaptic density, length of the synaptic active zone, postsynaptic density thickness, and synaptic gap width, was detected using transmission electron microscopy. RESULTS: We proved that sodium hydrosulfide (NaHS; a donor of H2S) significantly attenuated the depression-like behaviours and disorders of hippocampal synaptic plasticity in rotenone-induced PD rats. Furthermore, inhibition of the hippocampal Warburg effect by 2-deoxyglucose abolished NaHS-enhanced hippocampal synaptic plasticity and reversed NaHS-attenuated depression-like behaviours in the rotenone-induced PD rats. CONCLUSION: H2S attenuates PD-associated depression by improving the hippocampal synaptic plasticity in a hippocampal Warburg effect-dependent manner.