Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Drug Improves Cognitive Function in Mouse Model of Down Syndrome

Published: Wednesday, July 03, 2013
Last Updated: Wednesday, July 03, 2013
Bookmark and Share
The drug, an asthma medication called formoterol, strengthened nerve connections in the hippocampus.

It also improved contextual learning, in which the brain integrates spatial and sensory information.

Both hippocampal function and contextual learning, which are impaired in Down syndrome, depend on the brain having a good supply of the neurotransmitter norepinephrine. This neurotransmitter sends its signal via several types of receptors on the neurons, including a group called beta-2 adrenergic receptors.

“This study provides the initial proof-of-concept that targeting beta-2 adrenergic receptors for treatment of cognitive dysfunction in Down syndrome could be an effective strategy,” said Ahmad Salehi, MD, PhD, the study’s senior author and a clinical associate professor of psychiatry and behavioral sciences. The study was published online July 2 in Biological Psychiatry.

Down syndrome, which is caused by an extra copy of chromosome 21, results in both physical and cognitive problems. While many of the physical issues, such as vulnerability to heart problems, can now be treated, no treatments exist for poor cognitive function. As a result, children with Down syndrome fall behind their peers’ cognitive development. In addition, adults with Down syndrome develop Alzheimer’s-type pathology in their brains by age 40. Down syndrome affects about 400,000 people in the United States and 6 million worldwide.

In prior Down syndrome research, scientists have seen deterioration of the brain center that manufactures norepinephrine in both people with Down syndrome and its mouse model. Earlier work by Salehi’s team found that giving a norepinephrine precursor could improve cognitive function in a mouse model genetically engineered to mimic Down syndrome.

The new study refined this work by targeting only one group of receptors that respond to norepinephrine: the beta-2 adrenergic receptors in the brain. The researchers began by giving mice a compound that blocks the action of beta-2 adrenergic receptors outside the brain. They then gave the mice formoterol, a drug that can partially cross the blood-brain barrier and that was already known to activate beta-2 adrenergic receptors. Because people with Down syndrome are prone to heart problems, the researchers avoided activating a different group of norepinephrine-sensitive receptors, the beta-1 adrenergic receptors, which predominate in the heart.

The scientists saw improvement on a standard test of contextual learning in mice. In contextual learning, the brain integrates sensory and spatial information to remember the layout of a complex environment: for instance, a person using sounds, smells and sights to remember the location of a store in a shopping mall is using contextual learning. The researchers also saw more synapses and a more complex structure of dendrites, the nerves’ outgoing ends, in the hippocampus after the affected mice received formoterol.

“The fact that such a short period of giving medication can make these neurons much more complex is very interesting,” Salehi said, noting that mice in the study received the drug for a maximum of two weeks.

Further tests will be needed to determine whether formoterol might be an appropriate treatment for people with Down syndrome or whether to use another drug that activates the same receptors, Salehi said. The dose used in this study was many times higher than that used for asthma treatment, he cautioned, so it is not known whether it is safe. A lower dose might work, or other drugs that affect beta-2 adrenergic receptors might be safer and more effective in humans. Researchers also want to explore what parts of learning — taking in new information, remembering it or both — are affected by the drug treatment.

Prior research to improve cognitive function in children with Down syndrome has sometimes raised concerns from families that cognitive treatments would alter positive attributes of these children’s personalities, but Salehi said that is not the goal of his team’s research.

“Our aim is to enable these children to do better in school,” Salehi said. “It is absolutely not to change their personalities or the way they react to society.” Changing a child’s personality would be much more complicated than activating a subgroup of receptors in the brain, he said.

Salehi’s team and collaborators at Stanford included Van Dang, DVM, PhD, a postdoctoral scholar in psychiatry and behavioral sciences; Rachel Nosheny, PhD, a postdoctoral scholar in molecular and cellular physiology; and John Wesson Ashford, MD, PhD, a clinical professor of psychiatry and behavioral sciences. All researchers except Nosheny are affiliated with both the Stanford University School of Medicine and the Veterans Affairs Palo Alto Health Care System.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,100+ scientific posters on ePosters
  • More Than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

$10M Grant Funds Infection-Focused Center
The new center will explore intracellular and intercellular processes by which salmonella bacteria, responsible for more than 100 million symptomatic infections annually, infect immune cells.
Wednesday, April 06, 2016
Resurrecting an Abandoned Drug
Previously discarded drug shows promise in helping human cells in a lab dish fight off two different viruses.
Wednesday, March 30, 2016
Fracking's Impact on Drinking Water Sources
A case study of a small Wyoming town reveals that practices common in the fracking industry may have widespread impacts on drinking water resources.
Wednesday, March 30, 2016
Imaging Cells and Tissues Under the Skin
First technique developed for viewing cells and tissues in three dimensions under the skin.
Tuesday, March 22, 2016
Glucose-Guzzling Immune Cells May Drive Coronary Artery Disease
Researchers at Stanford University have found excessive glucose uptake by inflammatory immune cells called macrophages, which reside in arterial plaques, may be behind coronary artery disease.
Wednesday, March 16, 2016
Ultra-Sensitive Test for Cancers, HIV
Test developed that is thousands of times more sensitive than current diagnostics.
Tuesday, March 15, 2016
Weighing up the Risk of Groundwater Contamination
Faulty, shallow wells can leak oil and natural gas into underground drinking-water supplies, Stanford Professor Rob Jackson finds.
Wednesday, February 24, 2016
Blood Test Could Transform TB Diagnosis
A simple blood test that can accurately diagnose active tuberculosis could make it easier and cheaper to control a disease that kills 1.5 million people every year.
Tuesday, February 23, 2016
Paper Published Based on RNA Game
Video-gamers have co-authored a paper describing a new set of rules for determining the difficulty of designing structures composed of RNA molecules.
Thursday, February 18, 2016
Marker Identifies Most Basic Form of Blood Stem Cell
Nearly 30 years after the discovery of the hematopoietic stem cell, Stanford researchers have found a marker that allows them to study the version of these stem cells that continues to replicate.
Wednesday, February 17, 2016
Flexible Gene Expression May Regulate Social Status
Scientists show how the selective expression of genes through epigenetics can regulate the social status of African cichlid fish.
Monday, January 11, 2016
World Forest Carbon Stocks Overestimated
Researchers with The Natural Capital Project show how fragmentation harms forests' ability to store carbon; more restoration is needed to reconnect forest patches.
Tuesday, January 05, 2016
U.S. Needs a New Approach for Governance of Risky Research
The United States needs better oversight of risky biological research to reduce the likelihood of a bioengineered super virus escaping from the lab or being deliberately unleashed, according three Stanford scholars.
Monday, January 04, 2016
Mapping the Mechanical Properties of Living Cells
Researchers have developed a new way to use atomic force microscopy to rapidly measure the mechanical properties of cells at the nanometer scale, an advance that could pave the way for better understanding immune disorders and cancer.
Monday, December 21, 2015
Viral Infections Leave a Signature on the Immune System
A test that queries the body’s own cells can distinguish a viral infection from a bacterial infection and could help doctors know when to use antibiotics.
Thursday, December 17, 2015
Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
World’s Largest Coral Gene Database
‘Genetic toolkit’ will help shed light on which species survive climate change.
A Boost for Regenerative Medicine
Growing tissues and organs in the lab for transplantation into patients could become easier after scientists discovered an effective way to produce three-dimensional networks of blood vessels, vital for tissue survival yet a current stumbling block in regenerative medicine.
Breast Cancer Drug Hope
A drug for breast cancer that is more effective than existing medicines may be a step closer thanks to new research.
Untangling Disease-Related Protein Misfolding
Work advances understanding of genetic forms of thrombosis, emphysema, cirrhosis of the liver, neurodegenerative diseases and inflammation, among others.
Early Genetic Changes in Premalignant Colorectal Tissue Identified
Findings point to drivers of early cancer development, targets for cancer prevention therapies.
Harnessing Nature’s Vast Array of Venoms for Drug Discovery
Scripps scientists have developed a method for rapidly identifying venoms.
Nanoparticles Target, Transform Fat Tissue
Nanoparticles designed to target white fat and convert it to calorie-burning brown fat slowed weight gain in obese mice without affecting food intake. This proof-of-concept work could lead to new therapies to treat obesity.
New Cancer Fighters Emerge From Lab
Rice University lab simplifies total synthesis of anti-cancer agent.
Scientists Find Evidence That Cancer Can Arise Changes
Researchers at Rockefeller University have found a mutation that affects the proteins that package DNA without changing the DNA itself can cause a rare form of cancer.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,100+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!