Kosel Filip, Torres Munoz Paula, Yang J Renee, Wong Aimee A, Franklin Tamara B
The Social Lab, Department of Psychology and Neuroscience, Dalhousie University, Halifax, B3H 4R2, Canada.
The Social Lab, Department of Psychology and Neuroscience, Dalhousie University, Halifax, B3H 4R2, Canada.
Behav Brain Res. 2019 Apr 19;362:160-172. doi: 10.1016/j.bbr.2019.01.029. Epub 2019 Jan 16.
In addition to memory impairments, patients with Alzheimer's disease (AD) exhibit a number of behavioural and psychological symptoms that can affect social interactions over the course of the disease. While altered social interactions have been demonstrated in a number of mouse models of AD, many models only recapitulate the initial stages of the disease, and these behavioural changes have yet to be examined over the course of disease progression. By performing a longitudinal study using the 5xFAD mouse model, we have demonstrated that transgenic females exhibit progressive alterations in social investigation compared to wild-type controls. Transgenic females exhibited an age-related reduction in interest for social odours, as well as reduced investigative behaviours towards novel conspecifics in a novel environment. However, transgenic mice exhibited no obvious olfactory deficits, nor any changes in scent-marking behaviour compared to wild-type controls, indicating that changes in investigative behaviour were due to motivation to engage with a social stimulus. This evidence suggests that transgenic 5xFAD females exhibit increased social anxiety in novel environments compared to wild-type controls. Overall, transgenic 5xFAD female mice mimic some features of social withdrawal observed in human AD patients suggesting this strain may be suitable for modelling aspects of the social dysfunction observed in human patients.
除了记忆障碍外，阿尔茨海默病（AD）患者还表现出一些行为和心理症状，这些症状在疾病过程中会影响社交互动。虽然在许多AD小鼠模型中都证实了社交互动的改变，但许多模型仅重现了疾病的初始阶段，而且这些行为变化尚未在疾病进展过程中进行研究。通过使用5xFAD小鼠模型进行纵向研究，我们证明与野生型对照相比，转基因雌性小鼠在社交探究方面表现出渐进性改变。转基因雌性小鼠对社交气味的兴趣随年龄增长而降低，在新环境中对新奇同种个体的探究行为也减少。然而，与野生型对照相比，转基因小鼠没有明显的嗅觉缺陷，气味标记行为也没有任何变化，这表明探究行为的改变是由于与社交刺激互动的动机。这一证据表明，与野生型对照相比，转基因5xFAD雌性小鼠在新环境中表现出更高的社交焦虑。总体而言，转基因5xFAD雌性小鼠模拟了人类AD患者中观察到的社交退缩的一些特征，表明该品系可能适合模拟人类患者中观察到的社交功能障碍的某些方面。
