Current molecular approaches to investigate pre‐synaptic dysfunction

Abstract

This is a Review for the special issue "Pre synaptic Dysfuntion and Disease". Abbreviations: abFP, acid brightening fluorescent protein; ADBE, activity-dependent bulk endocytosis; APEX, ascorbate peroxidase; BONCAT, biorthogonal noncanonical amino acid tagging; CLARITY, cleared lipid-extracted acryl-hybridized rigid immunostaining/in situ hybridization-compatible tissue hydrogel; CME, clathrin-mediated endocytosis; DAB, diaminobenzidine; dSTORM, direct stochastic optical reconstruction microscopy; EM, electron microscopy; FKBP, FK504-binding protein; FLIM, fluorescence lifetime imaging; FRB, FKBP-rapamycin binding; FRET, forster resonance energy transfer; GFP, green fluorescent protein; GRAB, G-protein coupled receptor activation based; HRP, horse radish peroxidase; iGluSnFR, intensity-based glutamate fluorescent reporter; iSnFR, intensity-based fluorescent reporter; miniSOG, mini singlet oxygen generator; mTOR, mammalian target of rapamycin; PALM, photo-activated localization microscopy; pH, potential of hydrogen; sdTIM, subdiffractional tracking of internalized molecules; SILAC, stable isotope labelling by amino acids in cell culture; SILAM, stable istope labelling in mammals; smFRET, single-molecule FRET; SNARE, soluble N-ethylmaleimide-sensitive factor Attachment Receptor; STED, stimulated emission depletion microscopy; uPAINT, universal point accumulation imaging in nanoscale topography; vGAT, vesicular gamma aminobutyric acid transporter; vGLUT, vesicular glutamate transporter.

Molecular mapping of neuronal architecture using STORM microscopy and new fluorescent probes for SMLM imaging

“…We could also use MemBright probes to label live brain (hippocampus, cortex, and cerebellum) or liver slices, allowing the labeling in depth and imaging using confocal or two photons microscopy 23 . Since our first paper in 2019, MemBright probes have been used by several other labs and cited in more than 60 articles and 39 reviews 29 – 57 It has been used in B lymphocytes, 58 in A431 cells, 59 and reused in neuronal cells to label growth cone and initial segments of hippocampal neurons, 60 presynaptic terminals, 29 and post-synaptic compartments 53 .…”

“…Since our first paper in 2019, MemBright probes have been used by several other labs and cited in more than 60 articles and 39 reviews 29 – 57 It has been used in B lymphocytes, 58 in A431 cells, 59 and reused in neuronal cells to label growth cone and initial segments of hippocampal neurons, 60 presynaptic terminals, 29 and post-synaptic compartments 53 . It has also been used to label apoptotic bodies (AB), microvesicles (MV), and small EV (sEV) isolated from MIN6 pancreatic beta cells exposed to inflammatory, hypoxic, or genotoxic stressors 61 .…”

Gut microbiome at the crossroad of genetic variants and behavior disorders

“…A traditional view is that, by directly impacting brain development and function, genetic variants are the primary drivers of the behavioral symptoms. Indeed, the genetic-risk loci are increasingly linked to parameters of neuroinflammation, neurogenesis, synaptic, or neurocircuit function, which are commonly viewed as fundamental to disease phenotypes 17 , 18 . However, given the inherent complex etiology of neuropsychiatric diseases, a major unanswered question is how the genetic variance may interact with other environmental factors underlying the complex behavioral phenotypes.…”

Preface to the Special Issue “Presynaptic Dysfunction and Disease”

“…Therefore, techniques that define protein targets, identify alterations to protein-protein interactions and pinpoint where these occur in the cell, are central to establishing both mechanism and phenotype. The integrated application of these approaches, as described by Harper and Smillie (2021), is key to resolving how presynaptic dysfunction may culminate in human disease.…”

“…This has highlighted a requirement to be able to interrogate the function and dysfunction of the presynapse in different models of human disease. Harper and Smillie (2021), discuss both established and emerging techniques to monitor presynaptic function with a particular emphasis on SV recycling. The range of independent approaches through which SV recycling can be investigated is relatively limited and most notably includes amphiphilic dyes, fluid phase markers, electrophysiology and genetically encoded reporters.…”