Protective Roles Of Valproate Sodium On Apoptosis Of Dopaminergic Neuron Induced By 6-OHDA

Aim:To study the protective roles of valproate sodium on apoptosis of dopaminergic neuron and SH-SY5Y cell line induced by 6-OHDA.Methods:Rat PD model was produced with stereotaxic administration of 6-OHDA into unilateral nigra.Effects of VPA on 6-OHDA-induced changes of TH and NF-κB protein expression in nigra were detected with immunohistochemistry.Effects of VPA on survival neuron of PD rats were determined with light microscope.Morphological changes of neuronal nucleus were observed with fluorchrome Hoechst33342.Effects of VPA on 6-OHDA-induced Bcl-2 downregulation were detected with Western blot analysis.Effects of VPA on 6-OHDA-induced changes of NF-κB p65 protein expression in SH-SY5Y cell line were detected with immunohistochemistry.Results:Immtmohistochemistry demonstrated that VPA blocked 6-OHDA-induced decreases in the number of TH posotive neurons and 6-OHDA-induced nuclear translocation of NF-κB p65. Microscopy revealed that the cell survival rate deceased in SH-SY5Y cells 24hr after injection of 6-OHDA.Pretreatment with VPA elevated cell survival rate and improve the cellular morphological changes.Hoechst33342 staining revealed that shrinkage,condense,fragmentation of chromatin occurred after injection of 6-OHDA.VPA inhibited the morphological changes.VPA inhibited 6-OHDA-induced Bcl-2 downregulation.Immunohistochemistry demonstrated that VPA blocked 6-OHDA-induced nuclear translocation of NF-κB p65 in SH-SYSY cell line.Conclusions:VPA has neuroprotective actions in against 6-OHDA-induced apoptotic death of rat nigra neurons and SH-SYSY cell line by inhibiting Bcl-2 and NF-κB-mediated signaling pathways.