Figure 7.

Schematic of pathology development and neurodegeneration as well as the effects of transgene suppression in the hippocampus of 208 TDP-43 Tg mice. (A) Expression of 208 TDP-43 CTF and the presence of pTDP-43 is detected from 2 weeks off Dox. (B) By 10–16 months off Dox, neurodegeneration occurs in the DG, and ubiquitin and mitochondria accumulate in the SLM region. (C) With 6 months back on Dox to suppress transgene expression, 208 TDP-43 CTF and pTDP-43 are cleared and selective DG neurodegeneration is ameliorated, despite continued presence of ubiquitin/mitochondria accumulations in the SLM. (D) However, by 19 months off Dox with continued 208 TDP-43 CTF expression, there is dramatic neurodegeneration in the DG.