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Target Concepts:
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Query: UMLS:C0002736 (
amyotrophic lateral sclerosis
)
19,048
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Coexistence of perseveration and apathy in the TDP-43
Q331K
knock-in mouse model of ALS-FTD. 3314 10
