Neuronal and glial hTDP-43 expression induces physiological impairment and toxicity with varying severity.

<p>(A) Flies expressing glial hTDP-43 display extreme locomotor impairment at 1–5 days post-eclosion in the Benzer fast phototaxis assay, while flies expressing neuronal hTDP-43 demonstrate a slight locomotor deficit in comparison to genetic controls (one-way ANOVA, p < 0.0001). This trend continues and is exacerbated by 5–10 days post-eclosion (one-way ANOVA, p < 0.0001). Four biological replicates performed for each experiment. (B) Lifespan analysis of flies expressing neuronal versus glial hTDP-43 in comparison to genetic controls. (C) Central projections of whole-mount brains reveals a stark increase in TUNEL-positive cells in flies expressing glial hTDP-43 in comparison to genetic controls at 5 days post-eclosion. <i>N</i> = 16 for <i>Repo</i> / + and <i>N</i> = 18 for <i>Repo</i> > hTDP-43. (D) TEM likewise reveals rampant apoptosis in the neuropil of flies expressing glial hTDP-43 at 12 days post-eclosion. Arrowheads indicate pro-apoptotic nuclei, as identified by morphology.