Instituto Cajal (CSIC), Madrid, Spain.
Hippocampus. 2011 Oct;21(10):1037-44. doi: 10.1002/hipo.20861. Epub 2010 Sep 16.
Why memory is a particular target for the pathological changes in Alzheimer's Disease (AD) has long been a fundamental question when considering the mechanisms underlying this disease. It has been established from numerous biochemical and morphological studies that AD is, at least initially, a consequence of synaptic malfunction provoked by Amyloid β (Aβ) peptide. APP/PS1 transgenic mice accumulate Aβ throughout the brain, and they have therefore been employed to investigate the effects of Aβ overproduction on brain circuitry and cognition. Previous studies show that Aβ overproduction affects spine morphology in the hippocampus and amygdala, both within and outside plaques (Knafo et al., (2009) Cereb Cortex 19:586-592; Knafo et al., (in press) J Pathol). Hence, we conducted a detailed analysis of dendritic spines located in the stratum oriens and stratum radiatum of the CA1 hippocampal subfield of APP/PS1 mice. Three-dimensional analysis of 18,313 individual dendritic spines revealed a substantial layer-specific decrease in spine neck length and an increase in the frequency of spines with a small head volume. Since dendritic spines bear most of the excitatory synapses in the brain, changes in spine morphology may be one of the factors contributing to the cognitive impairments observed in this AD model.
为什么记忆是阿尔茨海默病（AD）病理变化的特定靶点，当考虑这种疾病的发病机制时，这一直是一个基本问题。大量的生化和形态学研究已经证实，AD 至少最初是由淀粉样β（Aβ）肽引起的突触功能障碍的结果。APP/PS1 转基因小鼠在大脑中积累 Aβ，因此它们被用来研究 Aβ 过度产生对大脑回路和认知的影响。先前的研究表明，Aβ 过度产生会影响海马体和杏仁核内和外斑块中的棘突形态（Knafo 等人，（2009）Cereb Cortex 19:586-592；Knafo 等人，（即将出版）J Pathol）。因此，我们对 APP/PS1 小鼠 CA1 海马亚区的 stratum oriens 和 stratum radiatum 中的树突棘进行了详细分析。对 18313 个单独树突棘的三维分析显示，棘突颈部长度显著减少，棘突头部体积小的棘突频率增加。由于树突棘承载着大脑中大部分兴奋性突触，因此棘突形态的变化可能是导致该 AD 模型中观察到的认知障碍的因素之一。
