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Identification of Fluorescent Small Molecule Compounds for Synaptic Labeling by Image-Based, High-Content Screening. | LitMetric

AI Article Synopsis

  • The research addresses the challenge of noninvasive imaging of synapses in living brains, which typically requires genetically modified organisms or viral methods.
  • To tackle this, scientists developed a chemical method that uses small organic molecules to identify and label synaptic components in cultured cortical neurons.
  • They screened about 7,000 fluorescence dyes, discovering several compounds, particularly from the xanthone family, that effectively label synaptic structures, with one called CX-G3 showing promise for visualizing synaptic vesicles in brain tissue.

Article Abstract

Few tools are available for noninvasive imaging of synapses in the living mammalian brain. Current paradigms require the use of genetically modified mice or viral delivery of genetic material to the brain. To develop an alternative chemical approach, utilizing the recognition of synaptic components by organic small molecules, we designed an imaging-based, high-content screen in cultured cortical neurons to identify molecules based on their colocalization with fluorescently tagged synaptic proteins. We used this approach to screen a library of ∼7000 novel fluorescent dyes, and identified a series of compounds in the xanthone family that exhibited consistent synaptic labeling. Follow-up studies with one of these compounds, CX-G3, demonstrated its ability to label acidic organelles and in particular synaptic vesicles at glutamatergic synapses in cultured neurons and murine brain tissue, indicating the potential of this screening approach to identify promising lead compounds for use as synaptic markers, sensors, and targeting devices.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919986PMC
http://dx.doi.org/10.1021/acschemneuro.7b00263DOI Listing

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