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

Shashank Vasudevan, Janko Kajtez, Ada‐Ioana Bunea, Ana Gonzalez‐Ramos, Tania Ramos‐Moreno, Arto Heiskanen, Merab Kokaia, Niels Bent Larsen, Alberto Martínez‐Serrano, Stephan Sylvest Keller, Jenny Emnéus

Research output: Contribution to journalJournal articleResearchpeer-review

62 Downloads (Pure)

Abstract

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.
Original languageEnglish
Article number1902011
JournalAdvanced Science
Number of pages9
ISSN2198-3844
DOIs
Publication statusPublished - 2019

Cite this

@article{5c22b7c5d46347b78cf4c25b59042d4c,
title = "Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons",
abstract = "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.",
author = "Shashank Vasudevan and Janko Kajtez and Ada‐Ioana Bunea and Ana Gonzalez‐Ramos and Tania Ramos‐Moreno and Arto Heiskanen and Merab Kokaia and Larsen, {Niels Bent} and Alberto Mart{\'i}nez‐Serrano and Keller, {Stephan Sylvest} and Jenny Emn{\'e}us",
year = "2019",
doi = "10.1002/advs.201902011",
language = "English",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley",

}

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 Bent; Martínez‐Serrano, Alberto; Keller, Stephan Sylvest; Emnéus, Jenny.

In: Advanced Science, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons

AU - Vasudevan, Shashank

AU - Kajtez, Janko

AU - Bunea, Ada‐Ioana

AU - Gonzalez‐Ramos, Ana

AU - Ramos‐Moreno, Tania

AU - Heiskanen, Arto

AU - Kokaia, Merab

AU - Larsen, Niels Bent

AU - Martínez‐Serrano, Alberto

AU - Keller, Stephan Sylvest

AU - Emnéus, Jenny

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1002/advs.201902011

DO - 10.1002/advs.201902011

M3 - Journal article

C2 - 31871869

JO - Advanced Science

JF - Advanced Science

SN - 2198-3844

M1 - 1902011

ER -