Ketogenic diet affects substantia nigra TH, Bcl-2 and caspase-3 gene expressions in mouse models with 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine-induced PD

Objective To investigate the anti-apoptotic effect of ketogenic diet (KD) on substantia nigra dopaminergic neurons in mouse models with PD.Methods Eight-week-old male C57BL/6 mice, weighting 24-26 g, were randomly divided into normal diet and model group (1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine [MPTP]), experimental group (KD+MPTP), normal diet group and KD group. Mouse models with PD were established by subjecting them to intraperitoneal injection of MPTP. All the mice in the normal diet group and MPTP group were fed with normal diet and were free to access food, while mice in the KD+MPTP and KD group were fed with KD every other day for 1 month. All mice were trained for rotarod test during the feeding and time on the rotarod was formally recorded 1 d before the drug injection. One d after the last injection, rotarod test was implemented again, and then, samples of blood were collected for analysis of serum concentrations of ketone bodies and glucose. The levels of substantia nigra TH, Bcl-2 and caspase-3 gene expressions were examined by fluorescence quantitative PCR. Results The mice in the KD+MPTP group not only enjoyed a lower mortality rate, but also performed better in the rotarod test than mice in the MPTP group.The concentrations of serum ketone bodies in the KD group and KD+MPTP group were significantly higher than those in the other 2 groups (P＜0.05). Compared with the MPTP group, the levels of TH and Bcl-2 gene expressions in the KD+MPTP group were significantly increased, while the level of caspase-3 gene expression was significantly reduced (P＜0.05). Conclusion KD reverses the effect of MPTP administration by decreasing the level of Bcl-2 gene expression and increasing the level of caspase-3 gene expression, therefore, it inhibits the apoptosis of dopaminergic neurons and plays a vital role in the protection of substantia nigra dopaminergic neurons. Key words: Parkinson's disease;  Ketogenic diet;  1-methyl-4-phenyl 1,2,3,6tetrahydropyridine;  Bcl-2 gene;  Caspase-3 gene