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

- The expression of CBS and the level of endogenous hydrogen sulfide were markedly reduced in the SN in 6-OHDA-induced PD rats.
- The lentiviral vector of CBS overexpression increased CBS expression and production of endogenous hydrogen sulfide in 6-OHDA-induced PD rats.
- The lentiviral vector of CBS overexpression was able to reverse the behavioral motor deficits and neuronal loss induced by 6-OHDA and that these effects may be related to increasing the production of endogenous hydrogen sulfide with antioxidant effects.
- Manipulating CBS expression and endogenous H2S production may be a novel therapeutic strategy for the treatment of PD diseases.

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 α-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 α-synuclein(α-SYN) in the injured SN. NaHS (an H2S donor) had similar effects to CBS overexpression, 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.