Longitudinal assessment of aggression and circadian rhythms in the APPswe mouse model of Alzheimer`s disease

Bergamini, Giorgio; Massinet, Helene; Durkin, Sean; Steiner, Michel

doi:10.1016/j.physbeh.2022.113787

Cited by 3 publications

(2 citation statements)

References 66 publications

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“…Another study recently showed that the higher aggression levels of SAMP8 mice could still be observed at 12 months of age ( 24 ). This age-dependent increase in reactive aggressive behavior in SAMP8 contrasts with the progressive decline in aggressivity observed in another, transgenic, model of AD-related pathology [i.e., APPswe mice ( 31 )]. This suggests that SAMP8 mice, relative to other models of neurodegeneration and dementia, might better recapitulate the agitation/aggression-relevant behavioral neuropsychiatric disturbances occurring with increasing age and progressing brain pathology.…”

Section: Discussionmentioning

confidence: 62%

Probing the relevance of the accelerated aging mouse line SAMP8 as a model for certain types of neuropsychiatric symptoms in dementia

Bergamini

Massinet²,

Hart³

et al. 2023

Front. Psychiatry

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IntroductionPeople with dementia (PwD) often present with neuropsychiatric symptoms (NPS). NPS are of substantial burden to the patients, and current treatment options are unsatisfactory. Investigators searching for novel medications need animal models that present disease-relevant phenotypes and can be used for drug screening. The Senescence Accelerated Mouse-Prone 8 (SAMP8) strain shows an accelerated aging phenotype associated with neurodegeneration and cognitive decline. Its behavioural phenotype in relation to NPS has not yet been thoroughly investigated. Physical and verbal aggression in reaction to the external environment (e.g., interaction with the caregiver) is one of the most prevalent and debilitating NPS occurring in PwD. Reactive aggression can be studied in male mice using the Resident-Intruder (R-I) test. SAMP8 mice are known to be more aggressive than the Senescence Accelerated Mouse-Resistant 1 (SAMR1) control strain at specific ages, but the development of the aggressive phenotype over time, is still unknown.MethodsIn our study, we performed a longitudinal, within-subject, assessment of aggressive behaviour of male SAMP8 and SAMR1 mice at 4, 5, 6 and 7 months of age. Aggressive behaviour from video recordings of the R-I sessions was analysed using an in-house developed behaviour recognition software.ResultsSAMP8 mice were more aggressive relative to SAMR1 mice starting at 5 months of age, and the phenotype was still present at 7 months of age. Treatment with risperidone (an antipsychotic frequently used to treat agitation in clinical practice) reduced aggression in both strains. In a three-chamber social interaction test, SAMP8 mice also interacted more fervently with male mice than SAMR1, possibly because of their aggression-seeking phenotype. They did not show any social withdrawal.DiscussionOur data support the notion that SAMP8 mice might be a useful preclinical tool to identify novel treatment options for CNS disorders associated with raised levels of reactive aggression such as dementia.

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Section: Discussionmentioning

confidence: 62%

Probing the relevance of the accelerated aging mouse line SAMP8 as a model for certain types of neuropsychiatric symptoms in dementia

Bergamini

Massinet²,

Hart³

et al. 2023

Front. Psychiatry

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“…Females showed no in-cage aggression; conversely, aggressive behavior was detected among males (e.g., chasing and fighting), but it rarely led to death as long as only littermates were housed together after weaning. Thus, the resort to single housing is not necessary unlike other strains [71][72][73][74]. This is a crucial feature that pinpoints our model as a suitable mouse model for the study of AD.…”

Section: Discussionmentioning

confidence: 98%

Generation and Characterization of the First Murine Model of Alzheimer’s Disease with Mutated AβPP Inserted in a BALB/c Background (C.B6/J-APPswe)

Balietti

Casoli

Giorgetti

et al. 2023

JAD

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Background: Numerous mouse models of Alzheimer’s disease (AD) are available, but all suffer from certain limitations, thus prompting further attempts. To date, no one model exists with amyloidopathy in a BALB/c strain. Objective: To generate and characterize the C.B6/J-APP swe mouse, a model of AD with a mutated human gene for the amyloid-β protein precursor (AβPP) inserted in a BALB/c background. Methods: We analyzed five groups at different ages (3, 6, 9, 12, and 16–18 months) of C.B6/J-APP swe and wild-type mice (50% males and 50% females) for the main hallmarks of AD by western blotting, amyloid-β (Aβ) ELISA, immunocytochemistry, electrophysiology, and behavioral tests. Results: The C.B6/J-APP swe mouse displays early AβPP and Aβ production, late amyloid plaques formation, high level of tau phosphorylation, synaptic deficits (reduced density and functional impairment due to a reduced post-synaptic responsiveness), neurodegeneration caused by apoptosis and necroptosis/necrosis, microgliosis, astrocytic abnormalities, and sex-related differences in explorative behavior, anxiety-like behavior, and spatial long-term and working memories. Social housing is feasible despite the intra-cage aggressiveness of male animals. Conclusion: C.B6/J-APP swe mice develop most of the distinctive features of AD and is a suitable model for the study of brain atrophy mechanisms and of the differences between males and females in the onset of cognitive/non-cognitive deficits.

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The neural basis of neuropsychiatric symptoms in Alzheimer’s disease

Zhang,

Zhang

et al. 2024

Front. Aging Neurosci.

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Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy and aggression affect up to 90% of Alzheimer’s disease (AD) patients. These symptoms significantly increase caregiver stress and institutionalization rates, and more importantly they are correlated with faster cognitive decline. However, the neuronal basis of NPS in AD remains largely unknown. Here, we review current understanding of NPS and related pathology in studies of AD patients and AD mouse models. Clinical studies indicate that NPS prevalence and severity vary across different AD stages and types. Neuroimaging and postmortem studies have suggested that pathological changes in the anterior cingulate cortex, hippocampus, prefrontal cortex, and amygdala are linked to NPS, although the precise mechanisms remain unclear. Studies of AD mouse models have indicated that amyloid-beta and tau-related neurodegeneration in the hippocampus, prefrontal cortex, and anterior cingulate cortex are correlated with NPS-like behavioral deficits. A better understanding of the NPS phenotypes and related pathological changes will pave the way for developing a better management strategy for NPS in AD patients.

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Longitudinal assessment of aggression and circadian rhythms in the APPswe mouse model of Alzheimer`s disease

Cited by 3 publications

References 66 publications

Probing the relevance of the accelerated aging mouse line SAMP8 as a model for certain types of neuropsychiatric symptoms in dementia

Probing the relevance of the accelerated aging mouse line SAMP8 as a model for certain types of neuropsychiatric symptoms in dementia

Generation and Characterization of the First Murine Model of Alzheimer’s Disease with Mutated AβPP Inserted in a BALB/c Background (C.B6/J-APPswe)

The neural basis of neuropsychiatric symptoms in Alzheimer’s disease

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