Molecular probe specifically detects serotonin in fluorescence imaging
Serotonin in depression is
highly relevant in diagnosis, treatment, and drug development. To better
study this area, a Chinese team has now developed a fluorescent probe
for imaging processes that is highly sensitive and selective toward
serotonin. In the journal Angewandte Chemie, they also introduce
the preliminary results obtained from the cell and animal models.
© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
Depression represents a significant public health problem
around the world. Current treatments are insufficient, primarily because
it is difficult to determine the mechanism of depression. New studies
indicate that depression is not exclusively caused by decreased
serotonin levels.
To examine the role of serotonin in depression, a team led
by Weiying Lin at Guangxi University (China) wanted to develop a highly
selective molecular fluorescent probe. The problem with this is that
serotonin’s structure and chemistry closely resemble other
biomolecules, such as melatonin and tryptophan. However, precise
analyses have revealed subtle differences in reactivity. The team
designed a special reactive group (3-mercaptopropionate) that can react
very selectively with serotonin via a cascade reaction. They attached
this reactive building block to a fluorescent dye
(dicyanomethylene-benzopyran derivative).
Attachment of the “appendage” initially switches the probe
“off”. If it encounters serotonin, one section reacts first (SH group of
the reactive building block binds to a double bond in serotonin, thiol-ene
click reaction). Afterward, facilitated by proximity, a second bond is
formed (nucleophilic reaction between an amino group in serotonin and a
carbonyl group in the reactive building block). As a result, the
building block is removed from the fluorescent dye and its fluorescence
is switched “on”. The probe selectively and sensitively indicates the
presence of serotonin, even inside cells.
The team used the probe to image a neuron cell line that
can be made into a model for depression by the administration of
corticosterone. It turned out that the serotonin level in the normal and
“depressed” cells was nearly equally high. However, the depressive cells
were able to expel significantly less serotonin in response to
stimulation. Administration of the current antidepressive drugs
(serotonin reuptake inhibitors) slightly increased the release.
According to a hypothesis, mTOR, a biomolecule that plays a
role in many cellular signaling pathways, could be related to a reduced
ability to release serotonin. The team observed that with the mTOR
activators, the serotonin release in the depressive cells was
significantly increased, while the mTOR inhibitors reduce serotonin
release from the normal cells. All results could be confirmed in the
neuron and mouse models.
These imaging studies suggest that the serotonin level in
the model for depression is not the primary factor. The ability of
neurons to release serotonin seems far more critical. This ability
correlates strongly with the activity of mTOR, which could point the way
to advancement in the treatment of depression.
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About the Author
Dr. Weiying Lin is a Professor at Guangxi University. His research interests
cover the interdisciplinary areas of molecular recognition,
photochemistry, materials chemistry, analytical chemistry, and chemical
biology. He is a Fellow of the Royal Society of Chemistry.
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