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

Suspect Gene Corrupts Neural Connections

Published: Tuesday, August 19, 2014
Last Updated: Monday, August 18, 2014
Bookmark and Share
“Diseases of synapses” demo’d in a dish - NIH-funded study.

Researchers have long suspected that major mental disorders are genetically-rooted diseases of synapses - the connections between neurons. Now, investigators supported in part by the National Institutes of Health have demonstrated in patients’ cells how a rare mutation in a suspect gene disrupts the turning on and off of dozens of other genes underlying these connections.

“Our results illustrate how genetic risk, abnormal brain development and synapse dysfunction can corrupt brain circuitry at the cellular level in complex psychiatric disorders,” explained Hongjun Song, Ph.D. External Web Site Policy, of Johns Hopkins University, Baltimore, a grantee of the NIH’s National Institute of Mental Health (NIMH), a funder of the study.

Song and colleagues, from universities in the United States, China, and Japan, report on their discovery in the journal Nature, August 18, 2014.

“The approach used in this study serves as a model for linking genetic clues to brain development,” said NIMH director Thomas R. Insel, M.D.

Most major mental disorders, such as schizophrenia, are thought to be caused by a complex interplay of multiple genes and environmental factors. However, studying rare cases of a single disease-linked gene that runs in a family can provide shortcuts to discovery. Decades ago, researchers traced a high prevalence of schizophrenia and other major mental disorders - which often overlap genetically - in a Scottish clan to mutations in the gene DISC1 (Disrupted In Schizophrenia-1). But until now, most of what’s known about cellular effects of such DISC1 mutations has come from studies in the rodent brain.

To learn how human neurons are affected, Song’s team used a disease-in-a-dish technology called induced pluripotent stem cells (iPSCs). A patient’s skin cells are first induced to revert to stem cells. Stem cells play a critical role in development of the organism by transforming into the entire range of specialized cells which make up an adult. In this experiment, these particular “reverted” stem cells were coaxed to differentiate into neurons, which could be studied developing and interacting in a petri dish. This makes it possible to pinpoint, for example, how a particular patient’s mutation might impair synapses. Song and colleagues studied iPSCs from four members of an American family affected by DISC1-linked schizophrenia and genetically related mental disorders.

Strikingly, iPSC-induced neurons, of a type found in front brain areas implicated in psychosis, expressed 80 percent less of the protein made by the DISC1 gene in family members with the mutation, compared to members without the mutation. These mutant neurons showed deficient cellular machinery for communicating with other neurons at synapses.

The researchers traced these deficits to errant expression of genes known to be involved in synaptic transmission, brain development, and key extensions of neurons where synapses are located. Among these abnormally expressed genes were 89 previously linked to schizophrenia, bipolar disorder, depression, and other major mental disorders. This was surprising, as DISC1’s role as a hub that regulates expression of many genes implicated in mental disorders had not previously been appreciated, say the researchers.

The clincher came when researchers experimentally produced the synapse deficits by genetically engineering the DISC1 mutation into otherwise normal iPSC neurons - and, conversely, corrected the synapse deficits in DISC1 mutant iPSC neurons by genetically engineering a fully functional DISC1 gene into them. This established that the DISC1 mutation, was, indeed the cause of the deficits.

The results suggest a common disease mechanism in major mental illnesses that integrates genetic risk, aberrant neurodevelopment, and synapse dysfunction. The overall approach may hold promise for testing potential treatments to correct synaptic deficits, say the researchers.


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

New NIH-EPA Research Centers to Study Environmental Health Disparities
Scientists will partner with community organizations to study these concerns and develop culturally appropriate ways to reduce exposure to harmful environmental conditions.
Thursday, May 26, 2016
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.
Wednesday, May 25, 2016
Visual Impairment, Blindness Cases in U.S. Expected to Double by 2050
Researchers at NIH have suggested that there is a need for increased screening and interventions to identify and address treatable causes of vision loss.
Friday, May 20, 2016
Drug Might Help Treat Sepsis
A DNA enzyme called Top1 plays a key role in turning on genes that cause inflammation in mouse and human cells in response to pathogens. A drug blocking this enzyme rescued mice from lethal inflammatory responses, suggesting a potential treatment for sepsis.
Wednesday, May 18, 2016
NIH Funds New Studies on Ethical, Legal and Social Impact of Genomic Information
Four new grants from the National Institutes of Health will support research on the ethical, legal and social questions raised by advances in genomics research and the increasing availability of genomic information.
Wednesday, May 18, 2016
Large-scale HIV Vaccine Trial to Launch in South Africa
NIH-funded study will test safety, efficacy of vaccine regimen.
Wednesday, May 18, 2016
New HIV Vaccine Target Discovered
NIH-Led team have discovered a new vaccine target site on HIV.
Tuesday, May 17, 2016
Researchers Identify Genetic Links to Educational Attainment
Researchers at NIH have suggested that the large genetics analyses may be able to help discover biological pathways as well.
Thursday, May 12, 2016
Investigational Malaria Vaccine Protects Healthy U.S. Adults
Researchers at NIH have found that the malaria vaccine protected a small number of healthy, malaria-naïve adults in the U.S. from infection for more than one year after immunization.
Tuesday, May 10, 2016
Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Thursday, May 05, 2016
Finding Factors That Protect Against Flu
A clinical trial examining the body’s response to seasonal flu suggests new approaches for evaluating the effectiveness of seasonal flu vaccines.
Wednesday, April 27, 2016
Factors Influencing Influenza Vaccine Effectiveness Uncovered
The long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited, new research suggests.
Thursday, April 21, 2016
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Wednesday, April 20, 2016
Serotonin Transporter Structure Revealed
Researchers determined the 3-D structure of the serotonin transporter and visualized how two common antidepressants interact with the protein.
Wednesday, April 20, 2016
Improving Flu Vaccine Effectiveness
NIH study finds factors that may influence influenza vaccine effectiveness.
Wednesday, April 20, 2016
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.
New NIH-EPA Research Centers to Study Environmental Health Disparities
Scientists will partner with community organizations to study these concerns and develop culturally appropriate ways to reduce exposure to harmful environmental conditions.
Structure of Essential Digestive Enzyme Uncovered
Using a powerful combination of techniques from biophysics to mathematics, researchers have revealed new insights into the mechanism of a liver enzyme that is critical for human health.
Air Pollution Linked to Heart Disease
10-year project revealed air pollutants accelerate plaque build-up in arteries to the heart.
Getting a Better Look at How HIV Infects and Takes Over its Host Cells
A new approach, developed by a team of researchers led by The Rockefeller University and The Aaron Diamond AIDS Research Center (ADARC), offers an unprecedented view of how a virus infects and appropriates a host cell, step by step.
Following Tricky Triclosan
Antibacterial product flows through streams, crops.
Vitamin A May Help Improve Pancreatic Cancer Chemotherapy
The addition of high doses of a form of vitamin A could help make chemotherapy more successful in treating pancreatic cancer, according to an early study by Queen Mary University of London (QMUL).
Poverty Marks a Gene, Predicting Depression
New study of high-risk teens reveals a biological pathway for depression.
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.
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!