Real-Time Fast Scan Cyclic Voltammetry Detection and Quantification of Exogenously Administered Melatonin in Mice Brain

Abstract

Melatonin (MT) has been recently considered an excellent candidate for the treatment of sleep disorders, neural injuries, and neurological diseases. To better investigate the actions of MT in various brain functions, real-time detection of MT concentrations in specific brain regions is much desired. Previously, we have demonstrated detection of exogenously administered MT in anesthetized mouse brain using square wave voltammetry (SWV). Here, for the first time, we show successful detection of exogenous MT in the brain using fast scan cyclic voltammetry (FSCV) on electrochemically pre-activated carbon fiber microelectrodes (CFEs). In vitro evaluation showed the highest sensitivity (28.1 nA/μM) and lowest detection limit (20.2 ± 4.8 nM) ever reported for MT detection at carbon surface. Additionally, an extensive CFE stability and fouling assessment demonstrated that a prolonged CFE pre-conditioning stabilizes the background, in vitro and in vivo, and provides consistent CFE sensitivity over time even in the presence of a high MT concentration. Finally, the stable in vivo background, with minimized CFE fouling, allows us to achieve a drift-free FSCV detection of exogenous administered MT in mouse brain over a period of 3 min, which is significantly longer than the duration limit (usually < 90 s) for traditional in vivo FSCV acquisition. The MT concentration and dynamics measured by FSCV are in good agreement with SWV, while microdialysis further validated the concentration range. These results demonstrated reliable MT detection using FSCV that has the potential to monitor MT in the brain over long periods of time.

Electrically Controlled Neurochemical Delivery from Microelectrodes for Focal and Transient Modulation of Cellular Behavior

“…For example, sensory-evoked neural network activity in rat primary somatosensory cortex was studied by delivering GLU receptor antagonist, 6,7-Dinitroquinoxaline- 2,3-dione (DNQX) [ 5 ]. Neurochemical signals have been extensively reported when excitative or inhibitive drugs were injected to region of interest [ 6 , 7 , 8 ]. These studies rely on pharmacological perturbation to localized cell populations.…”

Molecular Mechanisms of Melatonin-Mediated Cell Protection and Signaling in Health and Disease

“…Melatonin is transported bound to the serum albumin in the blood, although it could be bound by hemoglobin as well [8,9]. It is capable of crossing the blood-brain barrier [10,11] and cellular membranes [12], and is found in high amounts in mitochondria within the cells [13,14].…”

Advances in Carbon-Based Microfiber Electrodes for Neural Interfacing

“…They have also been demonstrated with better stability when used for neural interfacing (Vomero et al, 2017;Nimbalkar et al, 2018;Vahidi et al, 2020). Among them, CF microelectrodes with small cross sections have been used for detection of neurotransmitters such as dopamine and serotine for over three decades in the brain using fast-scan cyclic voltammetry (Robinson et al, 2003;Dankoski and Wightman, 2013;Taylor et al, 2015;Castagnola et al, 2020). However, only recently they have been used for neural recording (Kozai et al, 2012(Kozai et al, , 2016Patel et al, 2015Patel et al, , 2016.…”