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Near-Infrared Ratiometric Fluorescent Probe for Detecting Endogenous Cu2+ in the Brain.

Jianping Zhu1, Marcus E Graziotto1, Veronica Cottam2

  • 1School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

ACS Sensors
|May 24, 2024
PubMed
Summary

A new fluorescent probe, CyCu1, accurately measures copper (Cu2+) in biological samples. This tool revealed lower copper levels in brain tissues of dementia with Lewy bodies patients, improving understanding of neurological disorders.

Keywords:
ArabidopsisLewy body diseaseactivity-based sensingcoppercyaninefluorescent probeneuroblastomaphotoacoustic imaging

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Medical Imaging

Background:

  • Copper is vital for nervous system function, and its dysregulation is linked to neurological diseases like Parkinson's and Alzheimer's.
  • Current methods for measuring intracellular copper lack sensitivity, hindering research into copper homeostasis in neuronal disorders.

Purpose of the Study:

  • To develop a sensitive, near-infrared (NIR) fluorescent probe for imaging intracellular copper (Cu2+) in biological systems.
  • To investigate the role of copper dysregulation in dementia with Lewy bodies (DLB) using the developed probe.

Main Methods:

  • Developed a reaction-based NIR ratiometric fluorescent probe, CyCu1, for Cu2+ detection.
  • Applied CyCu1 to image Cu2+ in cell cultures (SH-SY5Y), plant cells (Arabidopsis), and post-mortem DLB brain tissues.
  • Utilized CyCu1 for quantitative analysis of Cu2+ distribution in specific brain regions.

Main Results:

  • CyCu1 demonstrated high stability and selectivity, enabling effective Cu2+ imaging in various biological samples.
  • Significant reductions in Cu2+ levels were observed in the cytoplasm, neurons, and extracellular space of the substantia nigra in DLB patients compared to controls.
  • The probe also showed potential as a photoacoustic imaging agent for bimodal imaging applications.

Conclusions:

  • The CyCu1 probe is a valuable tool for sensitive intracellular copper imaging in biological and pathological contexts.
  • Cu2+ dysregulation in the substantia nigra is implicated in the neurodegeneration observed in dementia with Lewy bodies.
  • This research advances the understanding of copper's role in Lewy body disorders and offers potential for improved diagnostic imaging.