Work

Development of a Dual Fluorescent and Magnetic Resonance False Neurotransmitter That Reports Accumulation and Release from Dopaminergic Synaptic Vesicles

Year: 2021

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Myriad neuropsychiatric disorders are due to dopamine dysfunction. However, understanding these disorders is limited by our ability to measure dopamine storage and release. Fluorescent false neurotransmitters (FFNs), small-molecule dyes that co-transit through the synaptic vesicle cycle, have allowed us to image dopamine in cell culture and acute brain slice, but in vivo microscopy is constrained by the biopenetrance of light. Here, we adapt FFNs into magnetic resonance false neurotransmitters (MFNs). The design principles guiding MFNs are (1) the molecule is a valid false neurotransmitter and (2) it has a 19 F-substituent near a pH-sensing functional group, which (3) has p K a close to 6 so that the probe within vesicles is protonated. We demonstrate that MFN103 meets these criteria. While a magnetic resonance spectroscopy (MRS) signal was too low for measurement in vivo with the current technology, in principle, MFNs can quantify neurotransmitters within and without synaptic vesicles, which may underlie noninvasive in vivo analysis of dopamine neurotransmission.

Source: ACS Chemical Neuroscience

DOI: 10.1021/acschemneuro.1c00580

Authors: Michael R. Post, Wei-Li Lee, Jia Guo, Dalibor Sames, David Sulzer

Institutions: New York State Psychiatric Institute, Columbia University

Language: English

Topic: Molecular Sensors and Ion Detection

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,000