Exercise combined with induced pluripotent stem cells enhances the Wnt1-Lmx1a loop in the midbrain of Parkinsonian mice to alleviate Parkinsonian symptoms

Figure 1 Validation of Parkinson’s disease mouse model by rotarod test, open field test, and tyrosine hydroxylase immunohistochemistry. A: Rotarod latency in control group and Parkinson’s disease (PD) model group; B: Open-field test in control group and PD model group; C: Representative TH+ fiber staining in striatum (scale bars: 20 μm and 10 μm). ^cP < 0.01. Ctrl: Control group; PD: Parkinson’s disease group.

Figure 2 The results of rotarod test and open field test, as well as changes in serum epinephrine and nerve growth factor protein expression levels in mice of each group. A: The changes in the rotarod test performance of mice in each group; B: The changes in the open field test of sedentary and exercise Parkinson’s disease group; C: The enzyme-linked immunosorbent assay analysis of epinephrine in the serum of mice in each group; D: The enzyme-linked immunosorbent assay analysis of nerve growth factor in the serum of mice in each group. ^dP < 0.01. St: Sedentary Parkinson’s disease group; E: Exercise Parkinson’s disease group; T: Induced pluripotent stem cell-treated Parkinson’s disease group; ET: Exercise and induced pluripotent stem cell-treated Parkinson’s disease group; NGF: Nerve growth factor.

Figure 3 Immunofluorescence localization images of brain tissues from mice in sedentary Parkinson’s disease group, induced pluripotent stem cell-treated Parkinson’s disease group, and exercise and induced pluripotent stem cell-treated Parkinson’s disease group. A: Results of immunofluorescence staining of mouse brain tissue sections, blue: DAPI, green: OCT4; B: Relative expression of OCT4 in mouse brain tissue sections. ^cP < 0.05; ^dP < 0.01. St: Sedentary Parkinson’s disease group; T: Induced pluripotent stem cell-treated Parkinson’s disease group; ET: Exercise and induced pluripotent stem cell-treated Parkinson’s disease group.

Figure 4 Expression of Wnt1 and Lmx1a in the midbrain of mice in each group. A: The results of western blot detection of Wnt1 and Lmx1a in the midbrain of mice in each group; B: Statistical analysis of western blot results for Wnt1 and Lmx1a in the midbrain of mice in each group; C: Conduct reverse transcription polymerase chain reaction detection and analysis of Wnt1 in the midbrains of each group of mice; D: Carry out reverse transcription polymerase chain reaction detection and analysis of Lmx1a in the midbrains of each group of mice. ^cP < 0.05; ^dP < 0.01. St: Sedentary Parkinson’s disease group; E: Exercise Parkinson’s disease group; T: Induced pluripotent stem cell-treated Parkinson’s disease group; ET: Exercise and induced pluripotent stem cell-treated Parkinson’s disease group.

Figure 5 Expression of Neurog2 and TH in the midbrain of mice in each group. A: The results of western blot detection of Neurog2 and TH in the midbrain of mice in each group; B: Statistical analysis of western blot results for Neurog2 and TH in the midbrain of mice in each group; C: Reverse transcription polymerase chain reaction analysis results for Neurog2 in the midbrain of mice in each group; D: Reverse transcription polymerase chain reaction analysis results for TH in the midbrain of mice in each group. ^cP < 0.05; ^dP < 0.01. St: Sedentary Parkinson’s disease group; E: Exercise Parkinson’s disease group; T: Induced pluripotent stem cell-treated Parkinson’s disease group; ET: Exercise and induced pluripotent stem cell-treated Parkinson’s disease group.