Vibrating Tail, Digging, Body/Face Interaction, and Lack of Barbering: Sex-Dependent Behavioral Signatures of Social Dysfunction in 3xTg-AD Mice as Compared to Mice with Normal Aging

Torres–Lista, Virginia

doi:10.3233/jad-190253

Cited by 12 publications

(15 citation statements)

References 35 publications

(48 reference statements)

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“…Besides, the effect of chronic treatment with risperidone was evaluated in these behaviors since atypical antipsychotics are often chosen to treat BPSD symptoms, such as psychosis, aggression, and agitation. Risperidone exerted effects decreasing the anogenital behavior and in the case of the 3xTg-AD mice, it significantly corrected the preponderance of the vibrant behavior recently described as a characteristic of the social interaction pattern of female 3xTg-AD mice (Torres-Lista and Giménez-Llort, 2019). The effects of risperidone interacted with genotype in several variables of social behaviors studied, in such a way that the effects were more intense in the NTg genotype where risperidone decreased social behaviors, bringing them to levels equivalent to those 3xTg-AD groups.…”

Section: Discussionmentioning

confidence: 62%

“…Social interaction test . The SIT was found the most complete and sensitive tests to evaluate the deficits of social behavior among 3xTg-AD mice in comparison with those observed among NTg mice of the same age and sex (Torres-Lista and Giménez-Llort, 2019). Here, in the basal characterization before treatment, we replicated the results but, this time, evaluated within a behavioral battery.…”

Section: Discussionmentioning

confidence: 99%

“…Behavioral signatures of social dysfunction in 3xTg-AD mice were assessed by means of the SIT (File and Hyde, 1978) as recently described (Torres-Lista and Giménez-Llort, 2019). A dyad of two unfamiliar mice of the same genotype and sex were introduced in a standard home cage and video recorded for 5 min.…”

Section: Methodsmentioning

confidence: 99%

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Impact of Chronic Risperidone Use on Behavior and Survival of 3xTg-AD Mice Model of Alzheimer’s Disease and Mice With Normal Aging

2019

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Psychosis and/or aggression are common problems in dementia, and when severe or persistent, cause considerable patient distress and disability, caregiver stress, and early institutionalization. In 2005, the Food and Drug Administration (FDA) determined that atypical antipsychotics were associated with a significantly greater mortality risk compared to placebo, which prompted the addition of an FDA black-box warning. The American College of Neuropsychopharmacology (ACNP) White Paper, 2008, reviewed this issue and made clinical and research recommendations regarding the use of antipsychotics in dementia patients with psychosis and/or agitation. Increased mortality risk has also been described in cerebrovascular adverse events in elderly users of antipsychotics. In the present work, at the translational level, we used male 3xTg-AD mice (PS1M146V, APPSwe, tauP301L) at advanced stages of the disease reported to have worse survival than females, to study the behavioral effects of a low chronic dose of risperidone (0.1 mg/kg, s.c., 90 days, from 13 to 16 months of age) and its impact on long-term survival, as compared to mice with normal aging. Animals were behaviorally assessed for cognitive and BPSD (behavioral and psychological symptoms of dementia)-like symptoms in naturalistic and experimental conditions (open-field test, T-maze, social interaction, Morris water maze, and marble test) before and after treatment. Weight, basal glucose levels, and IPGTT (i.p. glucose tolerance test) were also recorded. Neophobia in the corner test was used for behavioral monitoring. Survival curves were recorded throughout the experiment until natural death. The benefits of risperidone were limited, both at cognitive and BPSD-like level, and mostly restricted to burying, agitation/vibrating tail, and other social behaviors. However, the work warns about a clear early mortality risk window during the treatment and long-lasting impact on survival. Reduced life expectancy and life span were observed in the 3xTg-AD mice, but total lifespan (36 months) recorded in C57BL/6 × 129Sv counterparts with normal aging was also truncated to 28 months in those with treatment. Sarcopenia at time of death was found in all groups, but was more severe in wild-type animals treated with risperidone. Therefore, the 3xTg-AD mice and their non-transgenic counterparts can be useful to delimitate critical time windows and for studying the physio-pathogenic factors and underlying causal events involved in this topic of considerable public health significance.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

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Impact of Chronic Risperidone Use on Behavior and Survival of 3xTg-AD Mice Model of Alzheimer’s Disease and Mice With Normal Aging

2019

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“…To the best of our knowledge, only two studies have used mixed-sex groups to investigate social deficits. In both cases, aged 3xTg-AD mice (>12 months old) have shown female-specific differences in social engagement (Bories et al, 2012; Torres-Lista and Gimenez-Llort, 2019). Although our findings are corroborative with these studies, more work is required to understand the nature of socially relevant sex differences in AD.…”

Section: Discussionmentioning

confidence: 99%

Insoluble Aβ overexpression in an App knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, affecting anxiety-related behaviours

Pervolaraki

Hall

Foresteire

et al. 2019

Disease Models &Amp; Mechanisms

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We studied a new amyloid-beta precursor protein (App) knock-in mouse model of Alzheimer's disease (AppNL-G-F), containing the Swedish KM670/671NL mutation, the Iberian I716F mutation and the Artic E693G mutation, which generates elevated levels of amyloid beta (Aβ)40 and Aβ42 without the confounds associated with APP overexpression. This enabled us to assess changes in anxiety-related and social behaviours, and neural alterations potentially underlying such changes, driven specifically by Aβ accumulation. AppNL-G-F knock-in mice exhibited subtle deficits in tasks assessing social olfaction, but not in social motivation tasks. In anxiety-assessing tasks, AppNL-G-F knock-in mice exhibited: (1) increased thigmotaxis in the open field (OF), yet; (2) reduced closed-arm, and increased open-arm, time in the elevated plus maze (EPM). Their ostensibly anxiogenic OF profile, yet ostensibly anxiolytic EPM profile, could hint at altered cortical mechanisms affecting decision-making (e.g. ‘disinhibition’), rather than simple core deficits in emotional motivation. Consistent with this possibility, alterations in microstructure, glutamatergic-dependent gamma oscillations and glutamatergic gene expression were all observed in the prefrontal cortex, but not the amygdala, of AppNL-G-F knock-in mice. Thus, insoluble Aβ overexpression drives prefrontal cortical alterations, potentially underlying changes in social and anxiety-related behavioural tasks.

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“…In the assessment of the long-term effects of preventive/therapeutic interventions, risk factors, and hazards through different periods of our lives, the translational neuroscience approach benefits of the shorter life span of rodents as compared to humans is a key time frame that can be critical in this respect. Like in humans, housing conditions can have a significant impact on animal behavior, and this can also be important in those modeling diseases where social behavior is already impoverished ( 60 ). Using these advantages, we can explore in rodents the impact of social isolation or social restrictions due to social distance imposed by COVID-19 and in post-COVID scenarios in the most fragile elder population.…”

Section: Discussionmentioning

confidence: 99%

Impact of Social Isolation on the Behavioral, Functional Profiles, and Hippocampal Atrophy Asymmetry in Dementia in Times of Coronavirus Pandemic (COVID-19): A Translational Neuroscience Approach

Muntsant

Giménez-Llort

2020

Front. Psychiatry

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The impact of COVID-19 on the elderly is devastating, and nursing homes are struggling to provide the best care to the most fragile. The urgency and severity of the pandemic forces the use of segregation in restricted areas and confinement in individual rooms as desperate strategies to avoid the spread of disease and the worst-case scenario of becoming a deadly trap. The conceptualization of the post–COVID-19 era implies strong efforts to redesign all living conditions, care/rehabilitation interventions, and management of loneliness forced by social distance measures. Recently, a study of gender differences in COVID-19 found that men are more likely to suffer more severe effects of the disease and are over twice as likely to die. It is well-known that dementia is associated with increased mortality, and males have worse survival and deranged neuro-immuno-endocrine systems than females. The present study examines the impact of long-term isolation in male 3xTg-AD mice modeling advanced stages of Alzheimer's disease (AD) and as compared to age-matched counterparts with normal aging. We used a battery of ethological and unconditioned tests resembling several areas in nursing homes. The main findings refer to an exacerbated (two-fold increase) hyperactivity and emergence of bizarre behaviors in isolated 3xTg-AD mice, worrisome results since agitation is a challenge in the clinical management of dementia and an important cause of caregiver burden. This increase was consistently shown in gross (activity in most of the tests) and fine (thermoregulatory nesting) motor functions. Isolated animals also exhibited re-structured anxiety-like patterns and coping-with-stress strategies. Bodyweight and kidney weight loss were found in AD-phenotypes and increased by isolation. Spleen weight loss was isolation dependent. Hippocampal tau pathology was not modified, but asymmetric atrophy of the hippocampus, recently described in human patients with dementia and modeled here for the first time in an animal model of AD, was found to increase with isolation. Overall, the results show awareness of the impact of isolation in elderly patients with dementia, offering some guidance from translational neuroscience in these times of coronavirus and post–COVID-19 pandemic. They also highlight the relevance of personalized-based interventions tailored to the heterogeneous and complex clinical profile of the individuals with dementia and to consider the implications on caregiver burden.

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Vibrating Tail, Digging, Body/Face Interaction, and Lack of Barbering: Sex-Dependent Behavioral Signatures of Social Dysfunction in 3xTg-AD Mice as Compared to Mice with Normal Aging

Cited by 12 publications

References 35 publications

Impact of Chronic Risperidone Use on Behavior and Survival of 3xTg-AD Mice Model of Alzheimer’s Disease and Mice With Normal Aging

Impact of Chronic Risperidone Use on Behavior and Survival of 3xTg-AD Mice Model of Alzheimer’s Disease and Mice With Normal Aging

Insoluble Aβ overexpression in an App knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, affecting anxiety-related behaviours

Impact of Social Isolation on the Behavioral, Functional Profiles, and Hippocampal Atrophy Asymmetry in Dementia in Times of Coronavirus Pandemic (COVID-19): A Translational Neuroscience Approach

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