Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia; The Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia.
Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania, Australia.
Neurobiol Aging. 2022 Jul;115:29-38. doi: 10.1016/j.neurobiolaging.2022.03.007. Epub 2022 Mar 22.
Synaptic dysfunction is one of the key mechanisms associated with cognitive deficits observed in Alzheimer's disease (AD), yet little is known about the presynaptic axonal boutons in AD. Focusing on cortical en passant boutons (EPBs) along axons located in the motor, sensory and prefrontal regions of the cerebral cortex in the APP/PS1 mouse model of AD, we investigated structural properties of EPBs over the lifespan and in response to a midlife environmental enrichment (EE) intervention. At 3, 12, and 18-22 months and following 6 months of midlife EE, we found that EPBs showed remarkable resilience in preserving overall synaptic output, as evidenced by the maintained density of EPBs along the axon shaft across all experimental conditions. Using cranial window imaging to monitor synaptic changes in real time, we report that despite maintaining a stable synaptic density, the dynamic fraction (gains and losses) of EPBs was significantlyreduced at 10-13 months of age in APP/PS1 axons compared to age matched controls.
突触功能障碍是与阿尔茨海默病（AD）观察到的认知缺陷相关的关键机制之一，但人们对 AD 中的突触前轴突末梢知之甚少。本研究聚焦于 APP/PS1 小鼠 AD 模型大脑皮层运动、感觉和前额叶区域轴突上的皮质沿途末梢（EPBs），研究了 EPBs 在整个生命周期中的结构特性，并研究了中年环境富集（EE）干预的反应。在 3、12 和 18-22 个月以及中年 EE 干预 6 个月后，我们发现 EPBs 在保持整体突触输出方面表现出显著的弹性，这表现在沿轴突的 EPB 密度在所有实验条件下都保持稳定。使用颅窗成像实时监测突触变化，我们报告说，尽管保持稳定的突触密度，但与年龄匹配的对照组相比，APP/PS1 轴突中 EPB 的动态分数（增益和损耗）在 10-13 个月时显著降低。
