Department of Anatomy, School of Biomedical Sciences, Brain Research New Zealand, University of Otago, Dunedin, New Zealand.
Department of Anatomy, School of Biomedical Sciences, Brain Research New Zealand, University of Otago, Dunedin, New Zealand.
Brain Res. 2020 Nov 1;1746:147009. doi: 10.1016/j.brainres.2020.147009. Epub 2020 Jul 10.
Synapse dysfunction is an integral feature of Alzheimer's disease (AD) pathophysiology. In fact, prodromal manifestation of structural and functional deficits in synapses much prior to appearance of overt pathological hallmarks of the disease indicates that AD might be considered as a degenerative disorder of the synapses. Several research instruments and techniques have allowed us to study synaptic function and plasticity and their alterations in pathological conditions, such as AD. One such tool is the biochemically isolated preparations of detached and resealed synaptic terminals, the "synaptosomes". Because of the preservation of many of the physiological processes such as metabolic and enzymatic activities, synaptosomes have proved to be an indispensable ex vivo model system to study synapse physiology both when isolated from fresh or cryopreserved tissues, and from animal or human post-mortem tissues. This model system has been tremendously successful in the case of post-mortem tissues because of their accessibility relative to acute brain slices or cultures. The current review details the use of synaptosomes in AD research and its potential as a valuable tool in furthering our understanding of the pathogenesis and in devising and testing of therapeutic strategies for the disease.
突触功能障碍是阿尔茨海默病(AD)病理生理学的一个基本特征。事实上,突触的结构和功能缺陷在明显的疾病病理标志物出现之前就已经出现了前驱表现,这表明 AD 可能被认为是突触的退行性疾病。一些研究仪器和技术使我们能够研究突触功能和可塑性及其在病理条件下的变化,如 AD。一种这样的工具是分离和重新密封的突触末端的生化分离制备物,即“突触体”。由于保留了许多生理过程,如代谢和酶活性,突触体已被证明是一种不可或缺的离体模型系统,可用于研究从新鲜或冷冻保存的组织以及从动物或人类死后组织中分离的突触生理学。由于相对于急性脑切片或培养物而言,这种模型系统在死后组织中具有可及性,因此取得了巨大的成功。本综述详细介绍了突触体在 AD 研究中的应用及其作为一种有价值的工具的潜力,有助于我们了解发病机制,并设计和测试疾病的治疗策略。