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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 LU ; Ramos-Moreno, Tania LU orcid ; Heiskanen, Arto LU ; Kokaia, Merab LU ; Larsen, Niels B. ; Martínez-Serrano, Alberto and Keller, Stephan S. , et al. (2019) In Advanced Science 6(24).
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dopamine exocytosis, human neural stem cells, leaky optical fibers, optogenetics, pyrolysis
in
Advanced Science
volume
6
issue
24
article number
1902011
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85074093611
  • pmid:31871869
ISSN
2198-3844
DOI
10.1002/advs.201902011
language
English
LU publication?
yes
id
d2d55f18-5d4d-4ab2-9640-a22d206d109b
date added to LUP
2019-11-07 10:49:08
date last changed
2024-05-29 03:22:04
@article{d2d55f18-5d4d-4ab2-9640-a22d206d109b,
  abstract     = {{<p>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.</p>}},
  author       = {{Vasudevan, Shashank and Kajtez, Janko and Bunea, Ada Ioana and Gonzalez-Ramos, Ana and Ramos-Moreno, Tania and Heiskanen, Arto and Kokaia, Merab and Larsen, Niels B. and Martínez-Serrano, Alberto and Keller, Stephan S. and Emnéus, Jenny}},
  issn         = {{2198-3844}},
  keywords     = {{dopamine exocytosis; human neural stem cells; leaky optical fibers; optogenetics; pyrolysis}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{24}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Advanced Science}},
  title        = {{Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons}},
  url          = {{http://dx.doi.org/10.1002/advs.201902011}},
  doi          = {{10.1002/advs.201902011}},
  volume       = {{6}},
  year         = {{2019}},
}