Figure 2.

Increased Endogenous GDNF Level Improves Motor Learning in Old Gdnf^wt/hyper Mice

(A) Levels of Gdnf mRNA in the dorsal striatum (dSTR), substantia nigra (SN), and prefrontal cortex (PFC) of Gdnf^wt/wt and Gdnf^wt/hyper mice quantified by quantitative PCR and normalized to Actb expression level. Welch’s t test: p = 0.0039 (dSTR), p = 0.0015 (SN), and p = 0.0060 (PFC). (B) Animal body weight before (START) and after (END) experiments. Welch’s t test: p = 0.561 (START) and p = 0.666 (END). (C) Latency to fall in accelerating rotarod test. ANOVA comparing 15- to 17-month-old Gdnf^wt/wt and Gdnf^wt/hyper animals (black and red lines, respectively) revealed significant genotype effect (day 1: p = 0.295, day 2: p = 0.009). ANOVA comparing the performance between days 1 and 2 within the same group showed significant improvement in Gdnf^wt/hyper animals (p = 0.017), but not in wild-type littermates (p = 0.081). The gray dotted line represents the rotarod performance of Gdnf^wt/hyper mice tested in Mätlik et al.³⁰ at 10 weeks of age. (D) Latency to turn in the vertical grid test at days 1 and 2 of the experiment. Welch’s t test comparing Gdnf^wt/wt and Gdnf^wt/hyper mice at day 1 (p = 0.041) and day 2 (p = 0.01). Paired Student’s t test comparing the latency to turn of Gdnf^wt/wt (p = 0.758) and Gdnf^wt/hyper mice (p = 0.049) at day 1 versus day 2. (E) Latency to reach the top of the grid in the vertical grid test. Welch’s t test: p = 0.037. (F) Latency to fall off the grid in the vertical grid test. Welch’s t test: p < 0.001. (A) dSTR and SN: n = 6 Gdnf^wt/wt and n = 7 Gdnf^wt/hyper; PFC: n = 7 Gdnf^wt/wt and n = 5 Gdnf^wt/hyper. (B–F) n = 25 Gdnf^wt/wt and n = 20 Gdnf^wt/hyper. Data are presented as mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. RR, rotarod; VG, vertical grid.