This critical review highlights significant technical advances and in vivo studies from the last five years that facilitate the development of diagnostic tools for brain disorders.
While the neurochemistry that underpins the behavioral phenotypes of depression is the subject of many studies, oxidative stress caused by the inflammation comorbid with depression has not adequately been addressed. In this study, we described novel antidepressant−antioxidant agents consisting of selenium-modified fluoxetine derivatives to simultaneously target serotonin reuptake (antidepressant action) and oxidative stress. Excitingly, we show that one of these agents (1-F) carries the ability to inhibit serotonin reuptake in vivo in mice. We therefore present a frontier dual strategy that paves the way for the future of antidepressant therapies.
Carbon
is the material of choice for electroanalysis of biological
systems, being particularly applicable to neurotransmitter analysis
as carbon fiber microelectrodes (CFMs). CFMs are most often applied
to dopamine detection; however, the scope of CFM analysis has rapidly
expanded over the last decade with our laboratory’s focus being
on improving serotonin detection at CFMs, which we achieved in the
past via Nafion modification. We began this present
work by seeking to optimize this modification to gain increased analytical
sensitivity toward serotonin under the assumption that exposure of
bare carbon to the in vivo environment rapidly deteriorates
analytical performance. However, we were unable to experimentally
verify this assumption and found that electrodes that had been exposed
to the in vivo environment were more sensitive to
evoked and ambient dopamine. We hypothesized that high in
vivo concentrations of ambient extracellular glutamate could
polymerize with a negative charge onto CFMs and facilitate response
to dopamine. We verified this polymerization electrochemically and
characterized the mechanisms of deposition with micro- and nano-imaging.
Importantly, we identified that the application of 1.3 V as a positive
upper waveform limit is a crucial factor for facilitating glutamate
polymerization, thus improving analytical performance. Critically,
information gained from these dopamine studies were extended to an in vivo environment where a 2-fold increase in sensitivity
to evoked serotonin was achieved. Thus, we present here the novel
finding that innate aspects of the in vivo environment
are auspicious for detection of dopamine and serotonin at carbon fibers,
offering a solution to our goal of an improved fast-scan cyclic voltammetry
serotonin detection paradigm.
Fast-scan
cyclic voltammetry (FSCV) at carbon fiber microelectrodes measures
low concentrations of analytes in biological systems. There are ongoing
efforts to simplify FSCV analysis, and several custom platforms are
available for filtering and multimodal analysis of FSCV signals, but
there is no single, easily accessible platform that has the capacity
for all of these features. Here we present The Analysis Kid: currently, the only free, open-source cloud application that does
not require a specialized runtime environment and is easily accessible via common browsers. We show that a user-friendly interface
can analyze multiplatform file formats to provide multimodal visualization
of FSCV color plots with digital background subtraction. We highlight
key features that allow interactive calibration and semiautomatic
parametric analysis via peak finding algorithms to
automatically detect the maximum amplitude, area under the curve,
and clearance rate of the signal. Finally, The Analysis Kid enables semiautomatic fitting of data with Michaelis–Menten
kinetics with single or dual reuptake models. The Analysis
Kid can be freely accessed at . The web application code is found, under an MIT license, at .
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.