减少了转基因 5xFAD 小鼠的社会调查并增加了伤害行为,Journal of Neuroscience Research

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减少了转基因 5xFAD 小鼠的社会调查并增加了伤害行为
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2020-01-07 , DOI: 10.1002/jnr.24578
Filip Kosel ₁ , Jacob S Hamilton ₁ , Sarah L Harrison ₁ , Victoria Godin ₁ , Tamara B Franklin ₁

Affiliation

社交退缩和激越/攻击性是阿尔茨海默病 (AD) 患者常见的痴呆症行为和心理症状，男性比女性表现出更多的攻击性行为。一些 AD 转基因小鼠模型也表现出社交退缩和攻击性，但其中许多模型仅概括了疾病的早期阶段。相比之下，AD 的 5xFAD 小鼠模型表现出快速、进行性的神经变性，适用于建模早期、中期和晚期疾病进展的认知和行为缺陷。传闻表明，与野生型对照相比，转基因 5xFAD 雄性表现出高水平的攻击性，但迄今为止，尚未研究该品系的间接遗传效应。我们测量了饲养在三种不同群居条件（仅转基因、仅野生型和混合基因型）中的 5xFAD 雄性的家笼行为以及当暴露于新的自由漫游或受限制的野生型时的社交接近行为。或转基因同种。尽管攻击行为的频率没有明显增加，但与仅野生型或混合基因型笼子相比，仅转基因的家笼由于攻击性造成的伤害需要更早分离。与野生型对照相比，转基因 5xFAD 雄性和雌性在研究自由漫游同种物种上花费的时间也更少，但它们显示出对受限制同种物种的正常研究；同种的基因型不影响接近行为，并且在转基因雄性中没有观察到攻击性。

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Reduced social investigation and increased injurious behavior in transgenic 5xFAD mice

Social withdrawal and agitation/aggression are common behavioral and psychological symptoms of dementia presented by Alzheimer's disease (AD) patients, with males exhibiting more aggressive behaviors than females. Some transgenic mouse models of AD also exhibit social withdrawal and aggression, but many of these models only recapitulate the early stages of the disease. By comparison, the 5xFAD mouse model of AD exhibits rapid, progressive neurodegeneration, and is suitable for modeling cognitive and behavioral deficits at early, mid‐, and late‐stage disease progression. Anecdotal reports suggest that transgenic 5xFAD males exhibit high levels of aggression compared to wild‐type controls, but to date, indirect genetic effects in this strain have not been studied. We measured home‐cage behaviors in 5xFAD males housed in three different group‐housing conditions (transgenic‐only, wild‐type only, and mixed‐genotype) and social approach behaviors when exposed to a novel free‐roaming or restrained, wild‐type or transgenic conspecific. Transgenic‐only home cages required earlier separation due to injuries arising from aggression compared to wild‐type‐only or mixed‐genotype cages, despite no obvious increase in the frequency of aggressive behaviors. Transgenic 5xFAD males and females also spent less time investigating free‐roaming conspecifics compared to wild‐type controls, but they showed normal investigation of restrained conspecifics; the genotype of the conspecific did not affect approach behavior, and there was no aggression observed in transgenic males. These findings provide evidence in an animal model that amyloid pathology ultimately leads to avoidance of novel social stimuli, and that frequent interactions between individuals exhibiting an AD phenotype further exacerbates aggressive behaviors.

更新日期：2020-01-07

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