Intrathecal and intracerebroventricular dopamine for Parkinson’s disease

Abraham, Mickey; Gold, Justin; Dondapati, Akhil; Gendreau, Julian; Mammis, Antonios; Herschman, Yehuda

doi:10.1016/j.clineuro.2020.106374

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…When developing targeted drug delivery to the brain, difficulties arise due to the presence of the blood–brain barrier [ 56 ]. The list of technologies that are currently used or being developed for targeted drug delivery to the brain includes: (i) intranasal administration of drugs and their delivery along the concentration gradient via the cranial nerves and vascular bundles into the brain, bypassing the blood–brain barrier [ 57 , 58 ], (ii) local reversible opening of the blood–brain barrier using ultrasound [ 59 ], (iii) drug administration into the cerebral ventricles near the target brain regions [ 60 ], and (iv) delivery of drugs directly to the pathological regions in the brain [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

A New Method for the Visualization of Living Dopaminergic Neurons and Prospects for Using It to Develop Targeted Drug Delivery to These Cells

Блохин

Lavrova

Surkov

et al. 2022

IJMS

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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.

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