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.

Leaky Opto-Electrical Neural Probe for Optical Stimulation and Electrochemical Detection of Dopamine Exocytosis

“…As shown in Figure 5C, the CVs display higher anodic peak currents compared to the cathodic peak currents. This behavior has previously been observed for measurement of dopamine with pyrolytic carbon electrodes [14] and is due to the quasi-reversible nature of dopamine electrochemistry. The peak separation for 50 µM dopamine at 100 mVs -1 was 90 mV.…”

A Heterostructure Coupling of Bioinspired, Adhesive Polydopamine, and Porous Prussian Blue Nanocubics as Cathode for High‐Performance Sodium‐Ion Battery

“…Dopamine, as a mussel‐inspired material containing catechol and amine groups, can be oxidized and self‐polymerized into polydopamine (PDA). [ 34–37 ] It is similar to the mussel protein, which can adhere to or coat on various kinds of material surfaces. [ 38–39 ] In particular, PDA has been investigated recently as coating layer on the electrode surface.…”

Manipulation of Stem Cells Fates: The Master and Multifaceted Roles of Biophysical Cues of Biomaterials

“…[ 103 ] Interventional optical fibers consisting of biodegradable polymers have been applied to solve the light penetration problem and accelerate the differentiation of hNSCs and hMSCs. [ 103,104 ] They accelerated bone regeneration when implanted into the bone injury site in vivo (Figure 5B).…”