Pre-administration of BAX-inhibiting peptides decrease the loss of the nigral dopaminergic neurons in rats

ABSTRACTAimsIn this study, we investigated the effects of Bax-inhibiting peptide (Bip)-V5, an anti-apoptosis membrane-permeable peptide, on the 6-hydroxydopamine (6-OHDA) induced Parkinson's disease (PD) model rats.Materials and methodsRats were randomly divided into five groups: Control, 6-OHDA only, Vehicle + 6-OHDA, zVAD + 6-OHDA, and V5 + 6-OHDA, that rats were preadministrated with different reagents before 6-OHDA administration.Key findingsThe result showed that intrastriatal preadministration of Bip-V5 significantly decreased the amphetamine-induced rotation of the 6-OHDA model rats and the loss of the nigral dopaminergic (DA) neurons. Moreover, Bip-V5 intrastriatal preadministration not only significantly decreased the expression of activated caspase 9 and activated caspase 3 but also decreased the enhanced expression of AIF and its nuclear translocation in the SNpc. The results in our study provide the first experimental evidence that both caspase-dependent and AIF-dependent apoptosis pathways are involved in the loss of the nigral DA neurons caused by intrastriatal administration of 6-OHDA, and intrastriatal preadministration of Bip-V5 can inhibit the above two apoptosis pathways to protect the nigral DA neurons.SignificanceOur results provide a new idea that Bax-inhibiting peptide may be a promising preventive or therapeutic method for PD.