Inhaled Hydrogen Sulfide Prevents Neurodegeneration and Movement Disorder in a Mouse Model of Parkinson's Disease

Abstract

Parkinson's disease is one of the major neurodegenerative disorders. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can cause Parkinson's disease–like symptoms and biochemical changes in humans and animals. Hydrogen sulfide (H₂S) has been shown to protect neurons. The goal of this study was to examine the effects of inhaled H₂S in a mouse model of Parkinson's disease induced by MPTP. Male C57BL/6J mice received MPTP at 80 mg/kg and breathed air with or without 40 ppm H₂S for 8 h/day for 7 days. Administration of MPTP induced movement disorder and decreased tyrosine hydroxylase (TH)-containing neurons in the substantia nigra and striatum in mice that breathed air. Inhalation of H₂S prevented the MPTP-induced movement disorder and the degeneration of TH-containing neurons. Inhaled H₂S also prevented apoptosis of the TH-containing neurons and gliosis in nigrostriatal region after administration of MPTP. The neuroprotective effect of inhaled H₂S after MPTP administration was associated with upregulation of genes encoding antioxidant proteins, including heme oxygenase-1 and glutamate-cysteine ligase. These observations suggest that inhaled H₂S prevents neurodegeneration in a mouse model of Parkinson's disease induced by MPTP, potentially via upregulation of antioxidant defense mechanisms and inhibition of inflammation and apoptosis in the brain. Antioxid. Redox Signal. 15, 343–352.