Skip to main content
. 2023 Apr 19;9(16):eade1282. doi: 10.1126/sciadv.ade1282

Fig. 2. Astrocytic TDP-43 alterations cause progressive memory loss.

Fig. 2.

(A) Schematic of the tet-off transgenic system used to induce astrocytic expression of hTDP-43 containing ΔNLS. E0, embryonic day 0. (B) Top rows: hTDP-43 (green) in hippocampal sections from 3-month-old NTG, hGFAP-tTA (tTA), and tetO–hTDP-43–ΔNLS (tetO) control mice or double transgenic ΔNLS mice. Scale bar, 200 μm. Bottom row: Total TDP-43 (green) and astrocyte marker GFAP (red). DAPI (blue) was used to visualize nuclei. Scale bar, 25 μm. (C) hTDP-43 in the hippocampal dentate gyrus (DG) and CA1 regions of ΔNLS mice. Graphs show the percentage of GFAP- or NeuN-immunoreactive cells that were also hTDP-43–positive. (D) hTDP-43 (green) in ΔNLS mice; astrocyte marker GFAP (magenta). Insets show magnified views. Scale bar, 300 μm. (E to N) Morris water maze testing at 3 to 4 (E to H) and 9 to 10 (I to N) months of age. (E) Distance traveled to reach target platform during hidden platform training. Repeated-measures two-way ANOVA: F(6,102) = 1.141, P = 0.344 for interaction and F(3,51) = 2.635, P = 0.0596 for genotype. (F to H) Probe trials. Durations in target and nontarget (other) quadrants. One-way ANOVA (target): F(3,49) = 0.06677, P = 0.9773 (F) and F(3,49) = 1.882, P = 0.1448 (G). Student’s t test with Welch’s correction: **P < 0.01 and ***P < 0.001 versus other. NS, no significant preference. (H) Swim paths during 72-hour probe; insets show magnified views of target. (I) Distance traveled during training. Repeated-measures two-way ANOVA: F(12,263) = 0.3298, P = 0.9834 for interaction and F(3,66) = 2.278, P = 0.0877 for genotype. (J to L) Probe trials. One-way ANOVA (target): F(3,66) = 5.372, P = 0.0023 (J) and F(3,65) = 3.548, P = 0.0192 (K); Dunnett’s test: ##P < 0.01 and ###P < 0.001 versus NTG target. Student’s t test with Welch’s correction: *P < 0.05, **P < 0.01, and ***P < 0.001 versus other. (L) Swim paths. (M and N) Probe trials. Student’s t test with Welch’s correction: *P < 0.05, **P < 0.01, and ***P < 0.001 versus other. (O) Novel object recognition (NOR) test. One-way ANOVA and Dunnett’s test: *P < 0.05 versus NTG.