Flanigan T J, Xue Y, Kishan Rao S, Dhanushkodi A, McDonald M P
Department of Neurology.
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN, USA.
Genes Brain Behav. 2014 Jun;13(5):488-500. doi: 10.1111/gbb.12133. Epub 2014 Apr 22.
A recent study reported lower anxiety in the 5xFAD transgenic mouse model of Alzheimer's disease, as measured by reduced time on the open arms of an elevated plus maze. This is important because all behaviors in experimental animals must be interpreted in light of basal anxiety and response to novel environments. We conducted a comprehensive anxiety battery in the 5xFAD transgenics and replicated the plus-maze phenotype. However, we found that it did not reflect reduced anxiety, but rather abnormal avoidance of the closed arms on the part of transgenics and within-session habituation to the closed arms on the part of wild-type controls. We noticed that the 5xFAD transgenics did not engage in the whisker-barbering behavior typical of mice of this background strain. This is suggestive of abnormal social behavior, and we suspected it might be related to their avoidance of the closed arms on the plus maze. Indeed, transgenic mice exhibited excessive home-cage social behavior and impaired social recognition, and did not permit barbering by wild-type mice when pair-housed. When their whiskers were snipped the 5xFAD transgenics no longer avoided the closed arms on the plus maze. Examination of parvalbumin (PV) staining showed a 28.9% reduction in PV+ inhibitory interneurons in the barrel fields of 5xFAD mice, and loss of PV+ fibers in layers IV and V. This loss of vibrissal inhibition suggests a putatively aversive overstimulation that may be responsible for the transgenics' avoidance of the closed arms in the plus maze.
最近的一项研究报告称，在阿尔茨海默病的5xFAD转基因小鼠模型中焦虑水平较低，这是通过高架十字迷宫开放臂上停留时间的减少来衡量的。这一点很重要，因为实验动物的所有行为都必须根据基础焦虑和对新环境的反应来解释。我们在5xFAD转基因小鼠中进行了一项全面的焦虑测试，并重复了十字迷宫表型。然而，我们发现这并没有反映出焦虑的降低，而是转基因小鼠异常地避开封闭臂，而野生型对照小鼠在实验过程中对封闭臂产生了习惯化。我们注意到5xFAD转基因小鼠没有表现出这种背景品系小鼠典型的胡须梳理行为。这表明存在异常的社会行为，我们怀疑这可能与它们在十字迷宫中避开封闭臂有关。事实上，转基因小鼠表现出过度的笼内社会行为和社会识别受损，与野生型小鼠成对饲养时不允许野生型小鼠梳理它们的胡须。当剪掉它们的胡须后，5xFAD转基因小鼠不再避开十字迷宫的封闭臂。小白蛋白（PV）染色检查显示，5xFAD小鼠桶状皮质中PV+抑制性中间神经元减少了28.9%，IV层和V层中PV+纤维缺失。这种触须抑制的丧失表明可能存在一种厌恶的过度刺激，这可能是转基因小鼠在十字迷宫中避开封闭臂的原因。
