Fig. 2
Effect of L444P GBA heterozygous mutation on the susceptibility of mice to MPTP-induced PD-like symptoms. a Representative photomicrographs from coronal mesencephalon sections containing TH-positive neurons in WT and GBA+/L444P mice treated with saline or MPTP, respectively (scale bar, 500 μm). b Stereology counts of TH and c Nissl-positive neurons in the SNpc region. Unbiased stereologic counting was performed for the SNpc region.) Representative photomicrograph of striatal sections stained for TH immunoreactivity with low (scale bar, 100 μm) and high magnification (scale bar, 50 μm). e Quantification of dopaminergic fiber densities in the striatum using Image J software (NIH). a-e Error bars represent the mean ± S.E.M (n = ten mice per group). Striatal DA and metabolites levels were measured by HPLC-ECD. Levels of f DA, g DOPAC, and h HVA in the striatum from WT and GBA+/L444P mice treated with saline or MPTP were measured. i DA turnover [(DOPAC + HVA/DA)] in the striatum was calculated. f-i Error bars represent the mean ± S.E.M (n = four mice per group). j Pole test was conducted on the sixth day post MPTP injection. Maximum time to climb down the pole was limited to 60 s. Error bars represent the mean ± S.E.M (n = fifteen mice per group). k Representative images of immunohistochemistry data for glial fibrillary acidic protein (GFAP, astrocyte specific marker) with low (scale bar, 100 μm) and high magnification (scale bar, 50 μm). l Intensities of GFAP positive signals in the SNpc of WT and GBA+/L444P mice treated with saline or MPTP were quantified and shown as a graph. k, l Error bars represent the mean ± S.E.M (ten mice per group). Two-way ANOVA was used for statistical analysis followed by post-hoc Bonferroni test for multiple group comparison. *P < 0.05, **P < 0.01, ***P < 0.001 vs. MPTP-treated WT group, or saline-treated WT and GBA+/L444P group. n.s: not significant