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 (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.

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

“…However, neuroprotective effects of H 2 S have been reported previously, not only in experimental models for Parkinson's disease, (21), vascular dementia (54) and homocysteineinduced neurotoxicity, but also in in vitro models for oxidative stress in neurons (55) and Alzheimer's disease (56). In an experimental mouse model for Parkinson's disease, inhalation of H 2 S prevents the devel- opment of neurodegeneration and movements disorders (20).…”

“…H 2 S also confers cytoprotection via suppression of inflammation (17) and by protecting mitochondrial function and integrity (17,18). Decreased levels of H 2 S in brain tissue are associated with neurodegenerative age-related diseases such as Parkinson's (19), and administration of H 2 S has been shown protective in experimental models for this disease (20)(21)(22). Decreased levels of CSE have recently been observed in human Huntington disease tissues and in a mouse Huntington model (22).…”

Gas Mediators in the Nervous System: Nitric Oxide, Hydrogen Sulfide and Carbon Monoxide

“…128 Farelerde oluşturulan Parkinson modelinde, H 2 S solutulması tirozin hidroksilaz içeren nöron kaybını azaltmış ve kliniği düzeltmiş olduğu ortaya konmuştur. 141 H 2 S'nin bu iyileştirici özellikleri göz önüne alı-narak, ACS84 adında H 2 S salan L-dopa derivesi olan bir bileşik geliştirilmiştir. 142 Bu bileşik 6-hidroksi dopaminle oluşacak hücre hasarı ve oksidatif strese karşı SH-SY5Y hücrelerini korumuştur.…”

Modes of Physiologic H2S Signaling in the Brain and Peripheral Tissues

“…An analysis of patient striata reveals diminished sulfhydration of parkin with reduced catalytic activity (90); whereas nitrosylation of parkin, which inactivates it, is elevated (14). H 2 S donors are protective in rodent models of PD and could offer avenues for therapeutics (30,39,48). Recently, we showed that H 2 S production is diminished in Huntington's disease (HD), which could play a role in the pathophysiology of the disease (68).…”