Fig. 3

Early loss of tyrosine hydroxylase positive neurons in the Cox10/DAT-cre mice. a dopamine quantification from striatal homogenates of 2-month-old animals normalized to mg of protein. b quantification of 3-MT, DOPAC and HVA from striatal homogenates normalized to mg of protein. c ratio of dopamine metabolites to dopamine content. (n = 4/group). This analysis shows drastic dopamine depletion in striata of Cox10/DAT-cre mice, as well as a decrease in dopamine metabolites. d Western blotting probing for TH and DAT in representative striatal homogenates of DAT-cre and Cox10/DAT-cre mice shows an undetectable presence of dopaminergic markers (actin for normalization). No changes in mitochondrial markers were detected (VDAC-porin, NDUFB8 (CI subunit), SDHB (CII subunit), UQCRC2 (core2 subunit of CIII), COXI (CIV subunit) and ATPase-α (CV subunit) (n = 4/group). e Representative immunohistochemical staining of TH in striata of 2-month-old animals (CTX = cortex, STR = striatum). f Representative immunohistochemical identification of TH+ neurons in midbrain sections of DAT-cre and Cox10/DAT-cre mice (black circles depict rare TH+ neuronal bodies). A massive neurodegeneration is already present at 2 months of age in Cox10/DAT-cre mice. g Immunohistochemical staining with anti-NeuN of hippocampus and cortex sections of 2-month-old DAT-cre and Cox10/DAT-cre mice shows no neurodegeneration in these regions. h: Western blot and relative quantification probing for NeuN and TUJ1 in cortical homogenates of 2-month-old DAT-cre and Cox10/DAT-cre mice. No changes in neuronal markers were detected in these regions. i: graphical representation of pathology progression of Cox10/DAT-cre mice. Scale bar = 50 μm. In all figures, error bars represent SEM. p values are indicated by asterisks (*p < 0.05, **p < 0.01, ***p < 0.001)