These authors contribute equally to this work.
Neuroprotective effects of hydrogen sulfide on Parkinson’s disease rat models
Article first published online: 23 DEC 2009
© 2010 The Authors. Journal compilation © Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland 2010
Volume 9, Issue 2, pages 135–146, April 2010
How to Cite
Hu, L.-F., Lu, M., Tiong, C. X., Dawe, G. S., Hu, G. and Bian, J.-S. (2010), Neuroprotective effects of hydrogen sulfide on Parkinson’s disease rat models. Aging Cell, 9: 135–146. doi: 10.1111/j.1474-9726.2009.00543.x
- Issue published online: 16 MAR 2010
- Article first published online: 23 DEC 2009
- Accepted for publication 4 December 2009
- hydrogen sulfide;
- metabolic inhibition;
- oxidative stress;
- Parkinson’s disease
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra (SN). The present study was designed to examine the therapeutic effect of hydrogen sulfide (H2S, a novel biological gas) on PD. The endogenous H2S level was markedly reduced in the SN in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Systemic administration of NaHS (an H2S donor) dramatically reversed the progression of movement dysfunction, loss of tyrosine-hydroxylase positive neurons in the SN and the elevated malondialdehyde level in injured striatum in the 6-OHDA-induced PD model. H2S specifically inhibited 6-OHDA evoked NADPH oxidase activation and oxygen consumption. Similarly, administration of NaHS also prevented the development of PD induced by rotenone. NaHS treatment inhibited microglial activation in the SN and accumulation of pro-inflammatory factors (e.g. TNF-α and nitric oxide) in the striatum via NF-κB pathway. Moreover, significantly less neurotoxicity was found in neurons treated with the conditioned medium from microglia incubated with both NaHS and rotenone compared to that with rotenone only, suggesting that the therapeutic effect of NaHS was, at least partially, secondary to its suppression of microglial activation. In summary, we demonstrate for the first time that H2S may serve as a neuroprotectant to treat and prevent neurotoxin-induced neurodegeneration via multiple mechanisms including anti-oxidative stress, anti-inflammation and metabolic inhibition and therefore has potential therapeutic value for treatment of PD.