Knafo Shira, Venero Cesar, Merino-Serrais Paula, Fernaud-Espinosa Isabel, Gonzalez-Soriano Juncal, Ferrer Isidro, Santpere Gabriel, DeFelipe Javier
Instituto Cajal (CSIC), Madrid, Spain.
J Pathol. 2009 Sep;219(1):41-51. doi: 10.1002/path.2565.
Patients with Alzheimer's disease (AD) suffer from impaired memory and emotional disturbances, the pathogenesis of which is not entirely clear. In APP/PS1 transgenic mice, a model of AD in which amyloid beta (Abeta) accumulates in the brain, we have examined neurons in the lateral nucleus of the amygdala (LA), a brain region crucial to establish cued fear conditioning. We found that although there was no neuronal loss in this region and Abeta plaques only occupy less than 1% of its volume, these mice froze for shorter times after auditory fear conditioning when compared to their non-transgenic littermates. We performed a three-dimensional analysis of projection neurons and of thousands of dendritic spines in the LA. We found changes in dendritic tree morphology and a substantial decrease in the frequency of large spines in plaque-free neurons of APP/PS1 mice. We suggest that these morphological changes in the neurons of the LA may contribute to the impaired auditory fear conditioning seen in this AD model.
阿尔茨海默病（AD）患者存在记忆障碍和情绪紊乱，其发病机制尚不完全清楚。在APP/PS1转基因小鼠（一种β淀粉样蛋白（Aβ）在大脑中积累的AD模型）中，我们检查了杏仁核外侧核（LA）中的神经元，LA是建立线索性恐惧条件反射的关键脑区。我们发现，尽管该区域没有神经元丢失，且Aβ斑块仅占其体积的不到1%，但与非转基因同窝小鼠相比，这些小鼠在听觉恐惧条件反射后僵住的时间更短。我们对LA中的投射神经元和数千个树突棘进行了三维分析。我们发现APP/PS1小鼠无斑块神经元的树突形态发生了变化，大棘突的频率大幅下降。我们认为，LA神经元的这些形态变化可能导致了该AD模型中出现的听觉恐惧条件反射受损。
