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. 2018 Feb 27;26(6):1552–1567. doi: 10.1016/j.ymthe.2018.02.022

Figure 5.

Figure 5

Neuroprotective Effect of TFEB Overexpression in the MPTP Mouse Model of Parkinson’s Disease

(A) Top: representative photomicrographs of tyrosine-hydroxylase-immunostained substantia nigra of MPTP-intoxicated mice previously injected with AAV-TFEB (n = 14) or vehicle (n = 10), and control mice treated with saline and previously injected with vehicle (n = 7). Scale bar, 200 μm. Bottom: stereological cell counts of dopaminergic neurons in substantia nigra pars compacta of all groups of animals; two-way ANOVA, post hoc Tukey’s. *p < 0.05 compared to control non-injected side. #p < 0.05 compared to control injected side. $p < 0.05 compared to MPTP+sham injected side. ˆp < 0.05 compared to MPTP+AAV-TFEB non-injected side. (B) Left: representative photomicrographs of tyrosine-hydroxylase-immunostained striata of MPTP-intoxicated mice previously injected with AAV-TFEB (n = 14) or vehicle (n = 10) and control mice treated with saline and previously injected with vehicle (n = 7). Scale bar, 500 μm. Right: optical densitometry of striatal TH-positive dopaminergic fibers of all groups of animals; two-way ANOVA, post hoc Tukey’s. *p < 0.05 compared to control non-injected side. #p < 0.05 compared to control injected side. +p < 0.05 compared to MPTP+sham non-injected side. $p < 0.05 compared to MPTP+sham injected side. ˆp < 0.05 compared to MPTP+AAV-TFEB non-injected side. (C) Average cell area of dopaminergic neurons of all groups of animals (n = 6–10 mice per group); two-way ANOVA, post hoc Tukey’s. *p < 0.05 compared to control non-injected side. #p < 0.05 compared to control injected side. $p < 0.05 compared to MPTP+sham injected side. ˆp < 0.05 compared to MPTP+AAV-TFEB non-injected side. (D) Cumulative rotations induced by systemic administration of amphetamine during 10-min intervals 14 days after the last administration of MPTP. The net contralateral rotations were obtained as follows: total left − total right 360° turns. The test was performed with MPTP-intoxicated mice previously injected with AAV-TFEB (n = 9) or vehicle (n = 13) and control mice treated with saline and previously stereotaxically injected with vehicle (n = 10); two-way ANOVA for repeated-measures, post hoc Tukey’s. *p < 0.05 compared to MPTP+sham. #p < 0.05 compared to control. (E) Striatal DA amount measured by microdialysis in the ipsilateral striatum following local amphetamine administration by reverse dialysis in MPTP-intoxicated mice (21 days after last MPTP injection) previously injected with AAV-TFEB (n = 5) or vehicle (n = 5) and control mice treated with saline and previously injected with vehicle (n = 7); two-way ANOVA for repeated-measures, post hoc Tukey’s. *p < 0.05 compared to control. #p < 0.05 compared to MPTP+sham. All data are represented as mean ± SEM.