The Study of Postmortem Human Synaptosomes for Understanding Alzheimer’s Disease and Other Neurological Disorders: A Review

被引:36
作者
Jhou J.-F. [1 ]
Tai H.-C. [1 ]
机构
[1] Department of Chemistry, National Taiwan University, Taipei
关键词
Brain bank; Neurochemistry; Neurodegeneration; Neuron; Subcellular fractionation; Synapse;
D O I
10.1007/s40120-017-0070-z
中图分类号
学科分类号
摘要
Synaptic dysfunction is thought to play important roles in the pathophysiology of many neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Over the past few decades, there have been systematic efforts to collect postmortem brain tissues via autopsies, leading to the establishment of dozens of human brain banks around the world. From cryopreserved human brain tissues, it is possible to isolate detached-and-resealed synaptic terminals termed synaptosomes, which remain metabolically and enzymatically active. Synaptosomes have become important model systems for studying human synaptic functions, being much more accessible than ex vivo brain slices or primary neuronal cultures. Here we review recent advances in the establishment of human brain banks, the isolation of synaptosomes, their biological activities, and various analytical techniques for investigating their biochemical and ultrastructural properties. There are unique insights to be gained by directly examining human synaptosomes, which cannot be substituted by animal models. We will also discuss how human synaptosome research has contributed to better understanding of neurological disorders, especially Alzheimer’s disease. © 2017, The Author(s).
引用
收藏
页码:57 / 68
页数:11
相关论文
共 93 条
  • [1] Eccles J.C., The synapse: from electrical to chemical transmission, Annu Rev Neurosci, 5, pp. 325-339, (1982)
  • [2] Tang Y., Nyengaard J.R., De Groot D.M., Gundersen H.J., Total regional and global number of synapses in the human brain neocortex, Synapse, 41, pp. 258-273, (2001)
  • [3] Hebb C.O., Whittaker V., Intracellular distributions of acetylcholine and choline acetylase, J Physiol, 142, pp. 187-196, (1958)
  • [4] Whittaker V., Michaelson I., Kirkland R.J.A., The separation of synaptic vesicles from nerve-ending particles (‘synaptosomes’), Biochem J, 90, pp. 293-303, (1964)
  • [5] De Robertis E., De I.A.P., Garnaiz G.R.D.L., Salganicoff L., Cholinergic and non-cholinergic nerve endings in rat brain. I. Isolation and subcellular distribution of acetylcholine and acetylcholinesterase, J Neurochem, 9, pp. 23-35, (1962)
  • [6] Gray E., Whittaker V., The isolation of nerve endings from brain: an electron microscopic study of cell fragments derived by homogenization and centrifugation, J Anat, 96, pp. 79-88, (1962)
  • [7] Whittaker V., The morphology of fractions of rat forebrain synaptosomes separated on continuous sucrose density gradients, Biochem J, 106, (1968)
  • [8] Jones D.G., Revell E., The postnatal development of the synapse: a morphological approach utilizing synaptosomes. I. General features, Z Zellforsch Mikrosk Anat, 111, pp. 179-194, (1970)
  • [9] Tai H.C., Wang B.Y., Serrano Pozo A., Frosch M.P., Spires-Jones T.L., Hyman B.T., Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer inverted question marks disease, Acta Neuropathol Commun, 2, (2014)
  • [10] Cotman C., Brown D.H., Harrell B.W., Anderson N.G., Analytical differential centrifugation: an analysis of the sedimentation properties of synaptosomes, mitochondria and lysosomes from rat brain homogenates, Arch Biochem Biophys, 136, pp. 436-447, (1970)