Featured Research

from universities, journals, and other organizations

Key to antidepressant response uncovered

Date:
February 7, 2013
Source:
Johns Hopkins Medicine
Summary:
Through a series of investigations in mice and humans, researchers have identified a protein that appears to be the target of both antidepressant drugs and electroconvulsive therapy. Results of their experiments explain how these therapies likely work to relieve depression by stimulating stem cells in the brain to grow and mature. In addition, the researchers say, these experiments raise the possibility of predicting individual people’s response to depression therapy, and fine-tuning treatment accordingly.

sFRP3 acts as a gatekeeper that links brain activity to new neuron growth. Proliferating progenitor neurons are shown in blue, immature neurons in green, and mature neurons in red.
Credit: Design by Max Song and Maggie Song

Through a series of investigations in mice and humans, Johns Hopkins researchers have identified a protein that appears to be the target of both antidepressant drugs and electroconvulsive therapy. Results of their experiments explain how these therapies likely work to relieve depression by stimulating stem cells in the brain to grow and mature. In addition, the researchers say, these experiments raise the possibility of predicting individual people's response to depression therapy, and fine-tuning treatment accordingly. Reports on separate aspects of the research were published in December on the Molecular Psychiatry website, and will also appear in the Feb. 7 issue of Cell Stem Cell.

"Previous studies have shown that antidepressants and electroconvulsive therapy both activate neural stem cells in the adult brain to divide and form new neurons," says Hongjun Song, Ph.D., a professor of neurology and director of the Stem Cell Program at the Johns Hopkins University School of Medicine's Institute for Cell Engineering. "What were missing were the specific molecules linking antidepressant treatment and stem cell activation."

To make that link, Song's team and its collaborators assembled a body of evidence from different types of experiments. In one, they compared gene activity in the brains of mice that had and had not been treated with electroconvulsive therapy, looking specifically at genes with protein products that are known to regulate neural stem cells. The comparison turned up differences in the activity of one inhibitor gene for a chemical chain reaction that had been previously implicated in stimulating neural stem cells. Specifically, the therapy reduced the amount of protein the inhibitor gene, sFRP3, produced, which would in turn have given the growth-stimulating chain reaction freer rein.

To learn more about sFRP3's effects, the team next compared normal mice with mice that had been engineered to lack the sFRP3 protein. They found that the modified mice behaved like normal mice on antidepressants; moreover, giving antidepressants to the modified mice did not further change their behavior. This strongly suggested that antidepressants work by blocking sFRP3; without sFRP3, the modified mice had nothing to block.

In order to tie their mouse work to what happens in the human brain, the researchers next analyzed genetic information from 541 depression patients and tracked their response to a course of antidepressant drugs. The team found three common variations in the human version of sFRP3 that were linked to a better response to therapy. Wondering what these variations actually did, the researchers searched a database that correlates gene sequences to gene activity in the human brain. All three variations caused less gene activity, they found, meaning that there likely would have been less inhibitor.

Song notes that sFRP3 is also regulated by other conditions, including exercise. "This gene's activity is very sensitive to the amount of activity in the brain, so sFRP3 seems to be a gatekeeper that links activity to new neuron growth," he says. The finding has two major near-term implications, he says: It could lead to genetic tests that enable doctors to predict a patient's response to antidepressants, and it provides a target for potential new therapies for the disease.

The studies were supported by the National Institute of Mental Health (grant numbers MH090115 and MH087874), the National Institute of Neurological Disorders and Stroke (grant numbers NS048271, NS047344 and NS080913), the National Institute of Child Health and Human Development (grant number HD069184), the National Institute of Environmental Health Sciences (grant number ES021957), the Brain & Behavior Research Foundation, the Maryland Stem Cell Research Fund, the International Mental Health Research Organization and the Max Planck Society.

Other authors on the Cell Stem Cell article are Mi-Hyeon Jang, Michael A. Bonaguidi, Yasuji Kitabatake, Jiaqi Sun, Juan Song, Eunchai Kang, Heechul Jun, Chun Zhong, Yijing Su, Junjie U. Guo, Marie Xun Wang, Kurt A. Sailor, Ju-Young Kim, Yuan Gao, Kimberly M. Christian and Guo-li Ming of the Johns Hopkins University School of Medicine. Other authors on the Molecular Psychiatry article are Mi-Hyeon Jang, Yasuji Kitabatake, Eunchai Kang, Heechul Jun, Mikhail V. Pletnikov, Kimberly M. Christian and Guo-li Ming of the Johns Hopkins University School of Medicine; René Hen of Columbia University; and Susanne Lucae and Elizabeth B. Binder of the Max Planck Institute of Psychiatry.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal References:

  1. Mi-Hyeon Jang, Michael A. Bonaguidi, Yasuji Kitabatake, Jiaqi Sun, Juan Song, Eunchai Kang, Heechul Jun, Chun Zhong, Yijing Su, Junjie U. Guo, Marie Xun Wang, Kurt A. Sailor, Ju-Young Kim, Yuan Gao, Kimberly M. Christian, Guo-li Ming, Hongjun Song. Secreted Frizzled-Related Protein 3 Regulates Activity-Dependent Adult Hippocampal Neurogenesis. Cell Stem Cell, 2013; 12 (2): 215 DOI: 10.1016/j.stem.2012.11.021
  2. M-H Jang, Y Kitabatake, E Kang, H Jun, M V Pletnikov, K M Christian, R Hen, S Lucae, E B Binder, H Song, G-I Ming. Secreted frizzled-related protein 3 (sFRP3) regulates antidepressant responses in mice and humans. Molecular Psychiatry, 2012; DOI: 10.1038/mp.2012.158

Cite This Page:

Johns Hopkins Medicine. "Key to antidepressant response uncovered." ScienceDaily. ScienceDaily, 7 February 2013. <www.sciencedaily.com/releases/2013/02/130207131342.htm>.
Johns Hopkins Medicine. (2013, February 7). Key to antidepressant response uncovered. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2013/02/130207131342.htm
Johns Hopkins Medicine. "Key to antidepressant response uncovered." ScienceDaily. www.sciencedaily.com/releases/2013/02/130207131342.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) — The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) — Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
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