Hydrogen sulphide attenuates neuronal apoptosis of substantia nigra by re‐establishing autophagic flux via promoting leptin signalling in a 6‐hydroxydopamine rat model of Parkinson's disease.

Previous studies reveal that hydrogen sulphide (H2S) exerts neuroprotection against neurotoxin‐induced Parkinson's disease (PD), but the underlying mechanism remains elusive. The present study was aimed to investigate whether H2S inhibits neuronal apoptosis of substantia nigra with the involvement of autophagy via promoting leptin signalling in 6‐hydroxydopamine (6‐OHDA)‐induced PD rats. In this study, neuronal apoptosis was analysed by TUNEL staining, the activity of caspase‐3 was measured by Caspase‐3 fluorometric assay kit, the expressions of Bax, Bcl‐2, Beclin‐1, LC3II, P62 and leptin were determined by Western blot analysis, and the numbers of autophagosomes and autolysosomes were assessed by transmission electron microscopy. Results showed that NaHS, a donor of exogenous H2S, mitigates 6‐OHDA‐induced the increases in the numbers of TUNEL‐positive cells, the activity of caspase‐3 and the expression of Bax, and attenuates 6‐OHDA‐induced a decrease in the expression of Bcl‐2 in substantia nigra of rats. In addition, 6‐OHDA enhanced the expressions of Beclin‐1, LC3‐II and P62, increased the number of autophagosomes, and decreased the number of autolysosomes in the substantia nigra, which were also blocked by administration of NaHS. Furthermore, NaHS reversed 6‐OHDA‐induced the down‐regulation of leptin expression in the substantia nigra, and treatment with leptin‐OBR, a blocking antibody of leptin receptor, attenuated the inhibition of NaHS on neuronal apoptosis and the improvement of NaHS on the blocked autophagic flux in substantia nigra of 6‐OHDA‐treated rats. Taken together, these results demonstrated that H2S attenuates neuronal apoptosis of substantia nigra depending on restoring impaired autophagic flux through up‐regulating leptin signalling in PD. [ABSTRACT FROM AUTHOR]