Open AccessNeuroprotective effects of hydrogen sulfide on Parkinson’s disease rat models
Author(s) -
Hu LiFang,
Lu Ming,
Tiong Chi Xin,
Dawe Gavin S.,
Hu Gang,
Bian JinSong
Publication year - 2010
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2009.00543.x
Subject(s) - rotenone , neuroprotection , substantia nigra , tyrosine hydroxylase , oxidative stress , neurotoxicity , striatum , neurodegeneration , pharmacology , parkinson's disease , microglia , neurotoxin , dopaminergic , nitric oxide , dopamine , neuroinflammation , biology , chemistry , inflammation , biochemistry , endocrinology , medicine , mitochondrion , immunology , toxicity , disease
Summary 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 (H 2 S, a novel biological gas) on PD. The endogenous H 2 S level was markedly reduced in the SN in a 6‐hydroxydopamine (6‐OHDA)‐induced PD rat model. Systemic administration of NaHS (an H 2 S 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. H 2 S 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 H 2 S 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.