| First Author | Kim E | Year | 2020 |
| Journal | Transl Psychiatry | Volume | 10 |
| Issue | 1 | Pages | 377 |
| PubMed ID | 33149110 | Mgi Jnum | J:306979 |
| Mgi Id | MGI:6718641 | Doi | 10.1038/s41398-020-01078-9 |
| Citation | Kim E, et al. (2020) Coexistence of perseveration and apathy in the TDP-43(Q331K) knock-in mouse model of ALS-FTD. Transl Psychiatry 10(1):377 |
| abstractText | Perseveration and apathy are two of the most common behavioural and psychological symptoms of dementia (BPSDs) in amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). Availability of a validated and behaviourally characterised animal model is crucial for translational research into BPSD in the FTD context. We behaviourally evaluated the male TDP-43(Q331K) mouse, an ALS-FTD model with a human-equivalent mutation (TDP-43(Q331K)) knocked into the endogenous Tardbp gene. We utilised a panel of behavioural tasks delivered using the rodent touchscreen apparatus, including progressive ratio (PR), extinction and visual discrimination/reversal learning (VDR) assays to examine motivation, response inhibition and cognitive flexibility, respectively. Relative to WT littermates, TDP-43(Q331K) mice exhibited increased responding under a PR schedule. While elevated PR responding is typically an indication of increased motivation for reward, a trial-by-trial response rate analysis revealed that TDP-43(Q331K) mice exhibited decreased maximal response rate and slower response decay rate, suggestive of reduced motivation and a perseverative behavioural phenotype, respectively. In the extinction assay, TDP-43(Q331K) mice displayed increased omissions during the early phase of each session, consistent with a deficit in activational motivation. Finally, the VDR task revealed cognitive inflexibility, manifesting as stimulus-bound perseveration. Together, our data indicate that male TDP-43(Q331K) mice exhibit a perseverative phenotype with some evidence of apathy-like behaviour, similar to BPSDs observed in human ALS-FTD patients. The TDP-43(Q331K) knock-in mouse therefore has features that recommend it as a useful platform to facilitate translational research into behavioural symptoms in the context of ALS-FTD. |
