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Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons

In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in s...

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Autores principales: Vasudevan, Shashank, Kajtez, Janko, Bunea, Ada‐Ioana, Gonzalez‐Ramos, Ana, Ramos‐Moreno, Tania, Heiskanen, Arto, Kokaia, Merab, Larsen, Niels B., Martínez‐Serrano, Alberto, Keller, Stephan S., Emnéus, Jenny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918109/
https://www.ncbi.nlm.nih.gov/pubmed/31871869
http://dx.doi.org/10.1002/advs.201902011
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author Vasudevan, Shashank
Kajtez, Janko
Bunea, Ada‐Ioana
Gonzalez‐Ramos, Ana
Ramos‐Moreno, Tania
Heiskanen, Arto
Kokaia, Merab
Larsen, Niels B.
Martínez‐Serrano, Alberto
Keller, Stephan S.
Emnéus, Jenny
author_facet Vasudevan, Shashank
Kajtez, Janko
Bunea, Ada‐Ioana
Gonzalez‐Ramos, Ana
Ramos‐Moreno, Tania
Heiskanen, Arto
Kokaia, Merab
Larsen, Niels B.
Martínez‐Serrano, Alberto
Keller, Stephan S.
Emnéus, Jenny
author_sort Vasudevan, Shashank
collection PubMed
description In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in significant adverse effects. Transplanting dopaminergic neurons derived from stem cells could restore dopamine levels without additional motor complications. However, the transplanted cells disperse in vivo and it is not possible to stimulate them on demand to modulate dopamine release to prevent dyskinesia. In order to address these issues, this paper presents a multifunctional leaky optoelectrical fiber for potential neuromodulation and as a cell substrate for application in combined optogenetic stem cell therapy. Pyrolytic carbon coated optical fibers are laser ablated to pattern micro‐optical windows to permit light leakage over a large area. The pyrolytic carbon acts as an excellent electrode for the electrochemical detection of dopamine. Human neural stem cells are genetically modified to express the light sensitive opsin channelrhodopsin‐2 and are differentiated into dopaminergic neurons on the leaky optoelectrical fiber. Finally, light leaking from the micro‐optical windows is used to stimulate the dopaminergic neurons resulting in the release of dopamine that is detected in real‐time using chronoamperometry.
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spelling pubmed-69181092019-12-23 Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons Vasudevan, Shashank Kajtez, Janko Bunea, Ada‐Ioana Gonzalez‐Ramos, Ana Ramos‐Moreno, Tania Heiskanen, Arto Kokaia, Merab Larsen, Niels B. Martínez‐Serrano, Alberto Keller, Stephan S. Emnéus, Jenny Adv Sci (Weinh) Full Papers In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in significant adverse effects. Transplanting dopaminergic neurons derived from stem cells could restore dopamine levels without additional motor complications. However, the transplanted cells disperse in vivo and it is not possible to stimulate them on demand to modulate dopamine release to prevent dyskinesia. In order to address these issues, this paper presents a multifunctional leaky optoelectrical fiber for potential neuromodulation and as a cell substrate for application in combined optogenetic stem cell therapy. Pyrolytic carbon coated optical fibers are laser ablated to pattern micro‐optical windows to permit light leakage over a large area. The pyrolytic carbon acts as an excellent electrode for the electrochemical detection of dopamine. Human neural stem cells are genetically modified to express the light sensitive opsin channelrhodopsin‐2 and are differentiated into dopaminergic neurons on the leaky optoelectrical fiber. Finally, light leaking from the micro‐optical windows is used to stimulate the dopaminergic neurons resulting in the release of dopamine that is detected in real‐time using chronoamperometry. John Wiley and Sons Inc. 2019-10-16 /pmc/articles/PMC6918109/ /pubmed/31871869 http://dx.doi.org/10.1002/advs.201902011 Text en © 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Vasudevan, Shashank
Kajtez, Janko
Bunea, Ada‐Ioana
Gonzalez‐Ramos, Ana
Ramos‐Moreno, Tania
Heiskanen, Arto
Kokaia, Merab
Larsen, Niels B.
Martínez‐Serrano, Alberto
Keller, Stephan S.
Emnéus, Jenny
Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons
title Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons
title_full Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons
title_fullStr Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons
title_full_unstemmed Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons
title_short Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons
title_sort leaky optoelectrical fiber for optogenetic stimulation and electrochemical detection of dopamine exocytosis from human dopaminergic neurons
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918109/
https://www.ncbi.nlm.nih.gov/pubmed/31871869
http://dx.doi.org/10.1002/advs.201902011
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