(Press-News.org) SAN ANTONIO (June 20, 2013) — A synthetic compound is able to turn off "secondary" vacuum cleaners in the brain that take up serotonin, resulting in the "happy" chemical being more plentiful, scientists from the School of Medicine at The University of Texas Health Science Center San Antonio have discovered. Their study, released June 18 by The Journal of Neuroscience, points to novel targets to treat depression.
Serotonin, a neurotransmitter that carries chemical signals, is associated with feelings of wellness. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that block a specific "vacuum cleaner" for serotonin (the serotonin transporter, or SERT) from taking up serotonin, resulting in more supply of the neurotransmitter in circulation in the extracellular fluid of the brain.
Delicate balance
"Serotonin is released by neurons in the brain," said Lyn Daws, Ph.D., professor of physiology and pharmacology in the School of Medicine. "Too much or too little may be a bad thing. It is thought that having too little serotonin is linked to depression. That's why we think Prozac-type drugs (SSRIs) work, by stopping the serotonin transporter from taking up serotonin from extracellular fluid in the brain."
A problem with SSRIs is that many depressed patients experience modest or no therapeutic benefit. It turns out that, while SSRIs block the activity of the serotonin transporter, they don't block other "vacuum cleaners." "Until now we did not appreciate the presence of backup cleaners for serotonin," Dr. Daws said. "We were not the first to show their presence in the brain, but we were among the first show that they were limiting the ability of the SSRIs to increase serotonin signaling in the brain. The study described in this new paper is the first demonstration of enhancing the antidepressant-like effect of an SSRI by concurrently blocking these backup vacuum cleaners."
Serotonin ceiling
Even if SERT activity is blocked, the backup vacuum cleaners (called organic cation transporters) keep a ceiling on how high the serotonin levels can rise, which likely limits the optimal therapeutic benefit to the patient, Dr. Daws said.
"Right now, the compound we have, decynium-22, is not an agent that we want to give to people in clinical trials," she said. "We are not there yet. Where we are is being able to use this compound to identify new targets in the brain for antidepressant activity and to turn to medicinal chemists to design molecules to block these secondary vacuum cleaners."
###
This work was supported by National Institutes of Health Grants R01-MH064489 (L.C.D.), R01-MH093320 (L.C.D., W.K.) and R03-MH086708 (G.G.G.), and a National Alliance for Research on Schizophrenia and Depression Independent Investigator Award (L.C.D.).
Decynium-22 Enhances SSRI-Induced Antidepressant-Like Effects in Mice: Uncovering Novel Targets to Treat Depression
Rebecca E. Horton 1 Deana M. Apple 1,2 W. Anthony Owens 1 Nicole L. Baganz 1 Sonia Cano 2 Nathan C. Mitchell 1 Melissa Vitela 1 Georgianna G. Gould 1 Wouter Koek 2,3* and Lynette C. Daws 1,3*
1 Departments of Physiology, 2 Psychiatry, and 3 Pharmacology, University of Texas Health Science Center, San Antonio, Texas 78229-3900
For current news from the UT Health Science Center San Antonio, please visit our news release website, like us on Facebook or follow us on Twitter.
About the UT Health Science Center San Antonio
The University of Texas Health Science Center at San Antonio, one of the country's leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health funding. The university's schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced approximately 28,000 graduates. The $736 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways "We make lives better®," visit http://www.uthscsa.edu.
Compound enhances SSRI antidepressant's effects in mice
2013-06-21
ELSE PRESS RELEASES FROM THIS DATE:
Geology: The deeper the rock the colder? Lava flow over snow? Plus other conundrums
2013-06-21
Boulder, Colo., USA – These ten new Geology articles confront geologic conundrums and capture evidence toward answering even the most difficult questions on topics such as strain localization; atmospheric CO2; ultra-high pressure metamorphism; white chalk cliffs; lithospheric dripping; retreating trenches; microbial diversity beneath glaciers and ice-sheets; salt-marsh ecosystems; New Zealand glaciers -- biggest well before Europe's Little Ice Age; rock mechanics; tsunami hazards; and tracking the impact of the 2011 Tohoku-oki earthquake.
Highlights are provided below. ...
A cheaper drive to 'cool' fuels
2013-06-21
University of Delaware chemist Joel Rosenthal is driven to succeed in the renewable energy arena.
Working in his lab in UD's Department of Chemistry and Biochemistry, Rosenthal and doctoral student John DiMeglio have developed an inexpensive catalyst that uses the electricity generated from solar energy to convert carbon dioxide, a major greenhouse gas, into synthetic fuels for powering cars, homes and businesses.
The research is published in the June 19 issue of the Journal of the American Chemical Society.
Gold and silver represent the "gold standard" in the world ...
Airborne gut action primes wild chili pepper seeds
2013-06-21
Scientists have long known that seeds gobbled by birds and dispersed across the landscape tend to fare better than those that fall near parent plants where seed-hungry predators and pathogens are more concentrated.
Now it turns out it might not just be the trip through the air that's important, but also the inches-long trip through the bird.
Seeds from a wild chili pepper plant found in South America, after being eaten and passed through the digestive tract of small-billed Elaenias, emerge with less of the odor that attracts seed-eating ants, and carrying fewer pathogens ...
Disney Research creates techniques for high quality, high resolution stereo panoramas
2013-06-21
Stereoscopic panoramas promise an inviting, immersive experience for viewers but, at high resolutions, distortions can develop that make viewing unpleasant or even intolerable. A team at Disney Research Zurich has found methods to correct these problems, yielding high-quality panoramas at megapixel resolutions.
The researchers will present findings related to their so-called Megastereo project at the IEEE Conference on Computer Vision and Pattern Recognition (CVPR), June 25-27, in Portland, Oregon.
Using software to digitally stitch overlapping images together into ...
Study shows a solitary mutation can destroy critical 'window' of early brain development
2013-06-21
JUPITER, FL, June 21, 2013 – Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown in animal models that brain damage caused by the loss of a single copy of a gene during very early childhood development can cause a lifetime of behavioral and intellectual problems.
The study, published this week in the Journal of Neuroscience, sheds new light on the early development of neural circuits in the cortex, the part of the brain responsible for functions such as sensory perception, planning and decision-making.
The research also pinpoints ...
Research reveals low exposure of excellent work by female scientists
2013-06-21
Scientists at the University of Sheffield have found that high quality science by female academics is underrepresented in comparison to that of their male counterparts.
The researchers analysed the genders of invited speakers at the most prestigious gatherings of evolutionary biologists in Europe - six biannual congresses of the European Society for Evolutionary Biology (ESEB) and found that male speakers outnumbered women.
Even in comparison to the numbers of women and men among world class scientists – from the world top ranked institutions for life sciences, and ...
A bit of good luck: A new species of burying beetle from the Solomon Islands Archipelago
2013-06-21
Scientists discovered a new species of burying beetle, Nicrophorus efferens. Burying beetles are well known to most naturalists because of their large size, striking black and red colors, and interesting reproductive behaviors - they bury small vertebrate carcasses which their offspring eat in an underground crypt, guarded by both parents. The study was published in the open access journal Zookeys.
This new species, known from only 6 specimens collected in 1968, sat unrecognized as an undescribed species for over 40 years. "It was a bit of good luck that led to our realization ...
Man's best friend
2013-06-21
Domestic dogs have been closely associated with humans for about 15,000 years. The animals are so well adapted to living with human beings that in many cases the owner replaces conspecifics and assumes the role of the dog's main social partner. The relationship between pet owners and dogs turns out to be highly similar to the deep connection between young children and their parents.
The importance of the owner to the dog
One aspect of the bond between humans and dogs is the so-called "secure base effect". This effect is also found in parent-child bonding: human infants ...
Potentially life-saving cooling treatment rarely used for in-hospital cardiac arrests
2013-06-21
PHILADELPHIA-- The brain-preserving cooling treatment known as therapeutic hypothermia is rarely being used in patients who suffer cardiac arrest while in the hospital, despite its proven potential to improve survival and neurological function, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the June issue of Critical Care Medicine. The authors suggest that scarce data about in-hospital cardiac arrest patients and guidelines that only call for health care providers to consider use of therapeutic hypothermia, rather than explicitly ...
When green algae run out of air
2013-06-21
When green algae "can't breathe", they get rid of excess energy through the production of hydrogen. Biologists at the Ruhr-Universität Bochum have found out how the cells notice the absence of oxygen. For this, they need the messenger molecule nitric oxide and the protein haemoglobin, which is commonly known from red blood cells of humans. With colleagues at the UC Los Angeles, the Bochum team reported in the journal "PNAS".
Haemoglobin – an old protein in a new look
In the human body, haemoglobin transports oxygen from the lungs to the organs and brings carbon dioxide, ...