Fig. 5.
Pimozide treatment did not improve TDP-43 pathology of TDP-43A315T mice. (a) Representative picture of human TDP-43 (red) and NeuN (green) in lumbar spinal cord sections. Nuclear/cytoplasmic localization of hTDP-43 was analyzed in 10 sections per mouse (n = 4 mice per group, two females and two males), and quantification is shown in the graph. No differences were observed in the nuclear localization of human TDP-43 after pimozide treatment (p = 0.312 by unpaired T test); data are mean ± sem, scale bar 50 μm. (b, c) Insoluble human TDP-43 was analyzed in lumbar spinal cord and cerebral cortex by western blot and normalized on Ponceau staining, i.e., total transferred proteins on the membrane, western blot, and quantification are shown. Pimozide treatment increased insoluble human TDP-43 in (b) lumbar spinal cord (n = 3 female mice per group, p = 0.010 by unpaired T test) and in (c) cerebral cortex (n = 3 female mice per group, p = 0.050 by Student T test); data are mean ± sem. (d) Representative picture of Iba1 staining in lumbar spinal cord. Number of events (cells/section) and body size of the cell were analyzed by ImageJ on 10 sections per mouse (n = 4 mice per group, two females and two males), and quantification is shown in the graph. No differences were observed in microglial activation after pimozide treatment (p = 0.749 for events and p = 0.196 for body size by unpaired T test), data are mean ± sem, scale bar=50 μm. (e) Astrocyte activation was analyzed by western blot in soluble fraction of lumbar spinal cord and normalized on Ponceau staining; western blot and quantification are shown. Pimozide treatment increased GFAP protein levels (n = 3 female mice per group, p = 0.038 by Student T test); data are mean ± sem