Extended Data Fig. 2: Dopamine imbalance and its impact on SST and NPY expression.
a, b) Total dopamine content in the striatum of TrkbPenk-KO decreases significantly by 8–9 months of age (−43%) after the initial increase at around three months (DA, 3.5 M vs 8–9 M, p = 0.007). However, DOPAC (−29%) and HVA (+38%) do not differ significantly between 3.5 M and 8–9 M (p = 0.1; p = 0.5, respectively). In controls, there is a slight decrease between 3.5 M and 8–9 M of age for DA content (−30%), p = 0.053; DOPAC (−10%), p = 0.64; and HVA (+58%), p = 0.37. Samples analysed are from Fig. 2a-b; 3.5 M, TrkbPenk-WT, n = 3; TrkbPenk-KO, n = 4. At 8–9 M, n = 4 for each group/genotype. c, d) Quantitative analysis of immunoreactive TH cell numbers in the SNc and VTA regions at 3 M. c) TH cell numbers in mutants indicate a significant increase in the SNc (TrkbPenk-WT, 3462 ± 182; TrkbPenk-KO, 4277 ± 269; *p = 0.036) as well as in the VTA (TrkbPenk-WT, 2156 ± 194.3; TrkbPenk-KO, 2932.6 ± 195.8; *p = 0.022); n = 5 each genotype, 3 females and 2 males. d) A representative epifluorescence image of a coronal section through the ventral midbrain shows TH immunofluorescence (green) in the SNc and VTA of TrkbPenk-WT mice. The SNc/VTA distinction was made following Allen’s mouse brain atlas. e–l) Representative IF images for SST and NPY at 3 M and 8 M of the whole dorsal striatum (SST, panels e, f and i, j; NPY, panels g, h and k, l) of TrkbPenk-WT and TrkbPenk-KO. Scale bars, f, j and h, l, 200μm; d, 50μm. VTA, ventral tegmental area; SNc, substantia nigra pars compacta. (a–c) Values are means ± SEM. p statistic from unpaired, two-tailed, Student’s t-test. Related to Fig. 2.
