Utilities of Isolated Nerve Terminals in Ex Vivo Analyses of Protein Translation in (Patho)physiological Brain States: Focus on Alzheimer's Disease

Abstract

Synapses are the cellular substrates of higher-order brain functions, and their dysfunction is an early and primary pathogenic mechanism across several neurological disorders. In particular, Alzheimer's disease (AD) is categorized by prodromal structural and functional synaptic deficits, prior to the advent of classical behavioral and pathological features. Recent research has shown that the development, maintenance, and plasticity of synapses depend on localized protein translation. Synaptosomes and synaptoneurosomes are biochemically isolated synaptic terminal preparations which have long been used to examine a variety of synaptic processes ex vivo in both healthy and pathological conditions. These ex vivo preparations preserve the mRNA species and the protein translational machinery. Hence, they are excellent in organello tools for the study of alterations in mRNA levels and protein translation in neuropathologies. Evaluation of synapse-specific basal and activity-driven de novo protein translation activity can be conveniently performed in synaptosomal/synaptoneurosomal preparations from both rodent and human brain tissue samples. This review gives a quick overview of the methods for isolating synaptosomes and synaptoneurosomes before discussing the studies that have utilized these preparations to study localized synapse-specific protein translation in (patho)physiological situations, with an emphasis on AD. While the review is not an exhaustive accumulation of all the studies evaluating synaptic protein translation using the synaptosomal model, the aim is to assemble the most relevant studies that have done so. The hope is to provide a suitable research platform to aid neuroscientists to utilize the synaptosomal/synaptoneurosomal models to evaluate the molecular mechanisms of synaptic dysfunction within the specific confines of mRNA localization and protein translation research.

Keywords: Activity-dependent; Alzheimer’s disease; Amyloid-beta; BDNF; Protein translation; Synaptoneurosomes; Synaptosomes.