Summary of the molecular, cellular, and behavioral changes in TDP-43 Tg+/+ mice as compared to the WT
| 2-mo Tg | 6-mo Tg | ||
| Cognitive functions | |||
| Water maze test | decrease | na | |
| Fear conditioning task | decrease | na | |
| Novel object recognition test | decrease | decrease | |
| Motor functions | |||
| Limb-clasping reflex | similar to WT | increase | |
| Rotarod testing | similar to WT | decrease | |
| LTP | decrease | na | |
| Gliosis | Anti-GFAP staining | na | increase |
| Expression levels of specific proteins | |||
| pERK | decrease | decrease | |
| pCREB | decrease | decrease | |
| GAD67 | increase | increase | |
| GFAP | increase | increase | |
| Presence on Western blot of urea-soluble fraction of the brain extracts | |||
| Polyubiquitinated TDP-43 | increase | prominent increase | |
| Phosphorylated TDP-43 | absence | absence | |
| 35 kD fragment of TDP-43 | increase | prominent increase | |
| 25 kD fragment of TDP-43 | absence | presence | |
| TDP-43+ NCIs adjacent to TDP-43 depleted nuclei in Tg mouse brain sections | Immunohistochemistry | absence | presence |
| Presence of TDP-43+, ubiquitin+ NCIs | Immunostaining | absence | presence |
| Hippocampus volume | MRI measurement | na | decrease |
| Neuronal loss | |||
| Brain weight | similar to WT | decrease | |
| Neuronal counts | similar to WT | decrease | |
| Apoptosis | TUNEL assay | absence | increase |
| 2-mo Tg | 6-mo Tg | ||
| Cognitive functions | |||
| Water maze test | decrease | na | |
| Fear conditioning task | decrease | na | |
| Novel object recognition test | decrease | decrease | |
| Motor functions | |||
| Limb-clasping reflex | similar to WT | increase | |
| Rotarod testing | similar to WT | decrease | |
| LTP | decrease | na | |
| Gliosis | Anti-GFAP staining | na | increase |
| Expression levels of specific proteins | |||
| pERK | decrease | decrease | |
| pCREB | decrease | decrease | |
| GAD67 | increase | increase | |
| GFAP | increase | increase | |
| Presence on Western blot of urea-soluble fraction of the brain extracts | |||
| Polyubiquitinated TDP-43 | increase | prominent increase | |
| Phosphorylated TDP-43 | absence | absence | |
| 35 kD fragment of TDP-43 | increase | prominent increase | |
| 25 kD fragment of TDP-43 | absence | presence | |
| TDP-43+ NCIs adjacent to TDP-43 depleted nuclei in Tg mouse brain sections | Immunohistochemistry | absence | presence |
| Presence of TDP-43+, ubiquitin+ NCIs | Immunostaining | absence | presence |
| Hippocampus volume | MRI measurement | na | decrease |
| Neuronal loss | |||
| Brain weight | similar to WT | decrease | |
| Neuronal counts | similar to WT | decrease | |
| Apoptosis | TUNEL assay | absence | increase |
na, not analyzed.