Cited 3 times in
Coexistence of perseveration and apathy in the TDP-43 Q331K knock-in mouse model of ALS-FTD
DC Field | Value | Language |
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dc.contributor.author | 김어수 | - |
dc.contributor.author | 이종은 | - |
dc.date.accessioned | 2020-12-01T18:03:39Z | - |
dc.date.available | 2020-12-01T18:03:39Z | - |
dc.date.issued | 2020-11 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/180571 | - |
dc.description.abstract | 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-43Q331K mouse, an ALS-FTD model with a human-equivalent mutation (TDP-43Q331K) 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-43Q331K 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-43Q331K 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-43Q331K 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-43Q331K mice exhibit a perseverative phenotype with some evidence of apathy-like behaviour, similar to BPSDs observed in human ALS-FTD patients. The TDP-43Q331K 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. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Nature Pub. Group | - |
dc.relation.isPartOf | TRANSLATIONAL PSYCHIATRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Coexistence of perseveration and apathy in the TDP-43 Q331K knock-in mouse model of ALS-FTD | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Psychiatry (정신과학교실) | - |
dc.contributor.googleauthor | Eosu Kim | - |
dc.contributor.googleauthor | Matthew A White | - |
dc.contributor.googleauthor | Benjamin U Phillips | - |
dc.contributor.googleauthor | Laura Lopez-Cruz | - |
dc.contributor.googleauthor | Hyunjeong Kim | - |
dc.contributor.googleauthor | Christopher J Heath | - |
dc.contributor.googleauthor | Jong Eun Lee | - |
dc.contributor.googleauthor | Lisa M Saksida | - |
dc.contributor.googleauthor | Jemeen Sreedharan | - |
dc.contributor.googleauthor | Timothy J Bussey | - |
dc.identifier.doi | 10.1038/s41398-020-01078-9 | - |
dc.contributor.localId | A00686 | - |
dc.contributor.localId | A03146 | - |
dc.relation.journalcode | J03952 | - |
dc.identifier.eissn | 2158-3188 | - |
dc.identifier.pmid | 33149110 | - |
dc.contributor.alternativeName | Kim, Eo Su | - |
dc.contributor.affiliatedAuthor | 김어수 | - |
dc.contributor.affiliatedAuthor | 이종은 | - |
dc.citation.volume | 10 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 377 | - |
dc.identifier.bibliographicCitation | TRANSLATIONAL PSYCHIATRY, Vol.10(1) : 377, 2020-11 | - |
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