Inhaled hydrogen sulfide prevents neurodegeneration and movement disorder in a mouse model of Parkinson's disease.
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 (H(2)S) has been shown to protect neurons. The goal of this study was to examine the effects of inhaled H(2)S 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 H(2)S 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 H(2)S prevented the MPTP-induced movement disorder and the degeneration of TH-containing neurons. Inhaled H(2)S also prevented apoptosis of the TH-containing neurons and gliosis in nigrostriatal region after administration of MPTP. The neuroprotective effect of inhaled H(2)S 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 H(2)S 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.
Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kotaro
K
Kida
Marina
M
Yamada
Kentaro
K
Tokuda
Eizo
E
Marutani
Manabu
M
Kakinohana
Masao
M
Kaneki
Fumito
F
Ichinose
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001522:Behavior, Animal; D015153:Blotting, Western; D001831:Body Temperature; D017931:DNA Primers; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000517:prevention & control*; D019636:Neurodegenerative Diseases / Q000517:prevention & control*; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006862:Hydrogen Sulfide