Neuroprotective effects of lentivirus-mediated cystathionine-beta-synthase overexpression against 6-OHDA-induced parkinson's disease rats

Parkinson's disease (PD) is age-related neurodegenerative disorder by a progressive loss of dopaminergic(DA) neurons in the substantia nigra (SN) and striatum, which is at least partly associated with a-synuclein protein accumulation in these neurons. Hydrogen sulfide (H2S) plays an important role in the nervous system. Studies have shown that H2S has a protective effect on PD. However, as a kind of gas molecules, H2S is lively, volatile, and not conducive to scientific research and clinical application. Cystathionine-beta-synthase(CBS) is the main enzymes of synthesis of H2S in the brain. In order to examine the neuroprotective effects of CBS on PD, we detected the effects of CBS overexpression on 6-Hydroxydopamine (6-OHDA)-lesioned PD rats using lentivirus-mediated gene transfection techniques. In the injured SN of 6-OHDA-induced PD rats, the CBS expression and the endogenous H2S level markedly decreased, while administration of lentivirus-mediated CBS overexpression increased the CBS expression and the endogenous H2S production.CBS overexpression dramatically reversed apomorphine-induced rotation of the 6-OHDA model rats, decreased the number of TUNEL-positive neurons and the loss of the nigral DA neurons, specifically inhibited 6-OHDA-induced oxidase stress injury, and down-regulated the expression of alpha-synuclein(alpha-SYN) in the injured SN. NaHS (an H2S donor) had similar effects to CBS over expression, while Amino-oxyacetate(AOAA, a CBS inhibitor) had opposite effects on PD rats. In summary, we demonstrated that CBS overexpression was able to provide neuroprotective on PD rats and improving the expression of CBS may be a potential therapeutic method for PD. (C) 2017 Published by Elsevier Ireland Ltd.