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

Research output: Contribution to journalArticle

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.

Details

Authors
Organisations
External organisations
  • Technical University of Denmark
  • Skåne University Hospital
  • Autonomous University of Madrid
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • dopamine exocytosis, human neural stem cells, leaky optical fibers, optogenetics, pyrolysis
Original languageEnglish
Article number1902011
JournalAdvanced Science
Publication statusE-pub ahead of print - 2019 Oct 16
Publication categoryResearch
Peer-reviewedYes