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- Title
A New Method for the Visualization of Living Dopaminergic Neurons and Prospects for Using It to Develop Targeted Drug Delivery to These Cells.
- Authors
Blokhin, Victor; Lavrova, Alina V.; Surkov, Sergey A.; Mingazov, Eduard R.; Gretskaya, Natalia M.; Bezuglov, Vladimir V.; Ugrumov, Michael V.
- Abstract
This is the first study aiming to develop a method for the long-term visualization of living nigrostriatal dopaminergic neurons using 1-(2-(bis(4-fluorophenyl)methoxy)ethyl)-4-(3-phenylpropyl)piperazine-BODIPY (GBR-BP), the original fluorescent substance, which is a derivative of GBR-12909, a dopamine uptake inhibitor. This method is based on the authors' hypothesis about the possibility of specifically internalizing into dopaminergic neurons substances with a high affinity for the dopamine transporter (DAT). Using a culture of mouse embryonic mesencephalic and LUHMES cells (human embryonic mesencephalic cells), as well as slices of the substantia nigra of adult mice, we have obtained evidence that GBR-BP is internalized specifically into dopaminergic neurons in association with DAT via a clathrin-dependent mechanism. Moreover, GBR-BP has been proven to be nontoxic. As we have shown in a primary culture of mouse metencephalon, GBR-BP is also specifically internalized into some noradrenergic and serotonergic neurons, but is not delivered to nonmonoaminergic neurons. Our data hold great promise for visualization of dopaminergic neurons in a mixed cell population to study their functioning, and can also be considered a new approach for the development of targeted drug delivery to dopaminergic neurons in pathology, including Parkinson's disease.
- Subjects
TARGETED drug delivery; DOPAMINE uptake inhibitors; DOPAMINERGIC neurons; FLUOROPHORES; PARKINSON'S disease; NORADRENERGIC neurons
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 7, p3678
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23073678