Featured Research

from universities, journals, and other organizations

New Role For Serotonin 'Ironed Out'

Date:
January 29, 2009
Source:
Vanderbilt University Medical Center
Summary:
Investigators have found a surprising link between brain iron levels and serotonin, a neurotransmitter involved in neuropsychiatric conditions ranging from autism to major depression. The new study also demonstrates the utility of a powerful in silico approach for discovering novel traits linked to subtle genetic variation.

Vanderbilt University Medical Center investigators have found a surprising link between brain iron levels and serotonin, a neurotransmitter involved in neuropsychiatric conditions ranging from autism to major depression.

Appearing in the Proceedings of the National Academy of Sciences the week of January 27, the study by Randy Blakely, Ph.D., and colleagues also demonstrates the utility of a powerful in silico approach for discovering novel traits linked to subtle genetic variation.

The serotonin transporter protein (SERT) regulates serotonin availability in the brain and periphery, and variations in human SERT have been linked to many neurobehavioral disorders – including alcoholism, depression, autism and obsessive-compulsive disorder. SERT is also a major target for medications like the selective serotonin reuptake inhibitors (SSRI) used for treating depression.

Thanks to a serendipitous mix-up in an animal order, Blakely and first author Ana Carneiro, Ph.D., discovered that a mouse strain they had been using to studying SERT function – called C57BL/6 – actually carries a mutation that reduces the function of the transporter.

"Importantly, low-functioning variants of human SERT have been associated with anxiety, depression, and reduced efficacy of SSRI medications," notes Blakely, senior author and director of the Vanderbilt Center for Molecular Neuroscience.

By querying an online resource called the Mouse Phenome Database, they found that most mouse strains possess a SERT version called "ER" – which is identical to the sequence found in human SERT. A small number of strains, however, including the commonly studied C57BL/6 strain, carry a different version (called "GK").

Carneiro realized that she could utilize her identification of SERT GK to elucidate new aspects of brain chemistry and behavior. Vanderbilt collaborator David Airey, Ph.D., helped Carneiro and Blakely exploit a separate panel of mice where the SERT GK variant is presented on many different genetic backgrounds – a so-called "recombinant inbred" population termed BXD mice.

Using lines from this population, the team found that SERT GK mice performed differently than SERT ER mice on tests of anxiety and depression, consistent with reduced function of SERT GK. Importantly, a public database of anatomical, biochemical and behavioral features exists for all mice in the BXD population, allowing Blakely and colleagues to identify novel traits linked with the low functioning SERT. From this in silico approach, Blakely and colleagues identified multiple trait differences affected by the SERT GK/ER variation, including traits associated with alcohol consumption and brain dopamine signaling.

Additionally, they found that iron levels in the brains of mice with the GK variant were significantly higher than in the ER variant mice. Iron is required to synthesize both serotonin and dopamine, and serotonin receptors are known to regulate iron-carrying proteins. But SERT had not been previously shown to control brain iron levels. Follow-up studies with mice where the SERT gene was eliminated (SERT "knock-out" mice) verified a critical role for the transporter in controlling brain iron levels.

"Because SERT is such an important drug target in treating anxiety, depression and OCD, we need to stop and think about how iron might be influencing these disorders," Blakely said. The study also demonstrates the power of an in silico approach – combined with traditional experimentation – in understanding how genes affect complex traits.

"The broader number of findings in our paper derives not from (experiments) we did, but from what the (scientific) community collectively did to populate the BXD database," Blakely noted.

"Indeed, this is a great example of how biostatistical approaches can help limit the amount of experimentation that is needed with animals."

Other authors included Brent Thompson and Chong-Bin Zhu, M.D., Ph.D., from Vanderbilt, and researchers from Nantong University, the University of Tennessee Heath Science Center, Oak Ridge National Laboratory and the University of North Carolina at Greensboro. The research was supported by the National Institutes of Health.

Blakely is also the Allan D. Bass Professor of Pharmacology and a professor of Pharmacology and of Psychiatry.


Story Source:

The above story is based on materials provided by Vanderbilt University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ana M. D. Carneiro, David C. Airey, Brent Thompson, Chong-Bin Zhu, Lu Lu, Elissa J. Chesler, Keith M. Erikson, and Randy D. Blakely. Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter-associated phenotypes. Proceedings of the National Academy of Sciences, 2009; DOI: 10.1073/pnas.0809449106

Cite This Page:

Vanderbilt University Medical Center. "New Role For Serotonin 'Ironed Out'." ScienceDaily. ScienceDaily, 29 January 2009. <www.sciencedaily.com/releases/2009/01/090127123009.htm>.
Vanderbilt University Medical Center. (2009, January 29). New Role For Serotonin 'Ironed Out'. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2009/01/090127123009.htm
Vanderbilt University Medical Center. "New Role For Serotonin 'Ironed Out'." ScienceDaily. www.sciencedaily.com/releases/2009/01/090127123009.htm (accessed July 28, 2014).

Share This




More Mind & Brain News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. Video provided by Newsy
Powered by NewsLook.com
University Quiz Implies Atheists Are Smarter Than Christians

University Quiz Implies Atheists Are Smarter Than Christians

Newsy (July 25, 2014) An online quiz from a required course at Ohio State is making waves for suggesting atheists are inherently smarter than Christians. Video provided by Newsy
Powered by NewsLook.com
Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins