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 3,500+ scientific posters on ePosters
  • More Than 5,000+ 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

Drug to Treat Alcohol Use Disorder Shows Promise Among Drinkers With High Stress
The findings suggest that potential future studies with drugs targeting vasopressin blockade should focus on populations of people with AUD who also report high levels of stress.
Friday, September 30, 2016
Monkeys Protected by Zika DNA Vaccine
Experimental Zika virus DNA vaccines successfully protected monkeys against Zika infection.
Thursday, September 29, 2016
Probe Identifies Schizophrenia Genes That Stunt Brain Development
Scientists have isolated schizophrenia-related gene variants that change gene expression in the brain.
Thursday, September 29, 2016
Developing Novel Ear Infection Treatments
Research team engineers antibiotic gel for treating middle ear infections.
Wednesday, September 28, 2016
“Sixth Sense” More Than a Feeling
NIH study of rare genetic disorder reveals importance of touch and body awareness.
Monday, September 26, 2016
“Sixth Sense” May Be More Than Just A Feeling
The NIH Study shows that two young patients with a mutation in the PIEZ02 have problems with touch and proprioception, or body awareness.
Friday, September 23, 2016
The Genetics of Blood Pressure
Researchers have identifed areas of the genome associated with blood-pressure including 17 previously unknown loci.
Wednesday, September 21, 2016
NIH Study Finds Link Between Depression, Gestational Diabetes
Researchers at NIH have discovered that the depression in early pregnancy doubles risk for gestational diabetes, and gestational diabetes increases risk for postpartum depression.
Tuesday, September 20, 2016
Detecting Bacterial Infections in Newborns
Researchers tested an alternative way to diagnose bacterial infections in infants—by analyzing RNA biosignatures from a small blood sample.
Wednesday, September 14, 2016
Finding Compounds That Inhibit Zika
Researchers identified compounds that inhibit the Zika virus and reduce its ability to kill brain cells.
Wednesday, September 14, 2016
Seeking Innovation to Combat Antimicrobial Resistance
Federal prize competition, with $20 million in prizes, seeks to develop new laboratory diagnostic tools to detect and distinguish antibiotic resistant bacteria.
Friday, September 09, 2016
Genetic Misdiagnoses of Heart Condition
Analysis found several genetic variations previously linked with a heart condition were harmless, leading to condition misdiagnosis.
Wednesday, September 07, 2016
Catalogue of Human Genetic Diversity Expands
The largest data set of human exomes to date has been assembled to better study seqence variants and their consequences.
Wednesday, September 07, 2016
Extreme Temperatures Could Increase Preterm Birth Risk
Researchers at NIH have found more preterm births among women exposed to extremes of hot and cold.
Friday, September 02, 2016
$12.4M Awarded to Neural Regeneration Projects
The National Institutes of Health will fund six projects to identify biological factors that influence neural regeneration.
Friday, September 02, 2016
Scientific News
Point of Care Diagnostics - A Cautious Revolution
Advances in molecular biology, coupled with the miniaturization and improved sensitivity of assays and devices in general, have enabled a new wave of point-of-care (POC) or “bedside” diagnostics.
Mass Spec Technology Drives Innovation Across the Biopharma Workflow
With greater resolving power, analytical speed, and accuracy, new mass spectrometry technology and techniques are infiltrating the biopharmaceuticals workflow.
One Step Closer to Precision Medicine for Chronic Lung Disease Sufferers
A study led by University of North Carolina at Chapel Hill, and National Jewish Health, has provided evidence of links between SNPs and known COPD blood protein biomarkers.
Charles River Acquires Agilux
Enhances Charles River’s early-stage capabilities in bioanalytical services.
Scientists Find Lethal Vulnerability in Treatment-Resistant Lung Cancer
The study describes how the drug Selinexor killed lung cancer cells and shrank tumors in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene.
How Baby’s Genes Influence Birth Weight And Later Life Disease
The large-scale study could help to target new ways of preventing and treating these diseases.
Genes Underlying Dogs’ Social Ability Revealed
The social ability of dogs is affected by genes that also seem to influence human behaviour, according to a new study from Linköping University in Sweden.
Drug to Treat Alcohol Use Disorder Shows Promise Among Drinkers With High Stress
The findings suggest that potential future studies with drugs targeting vasopressin blockade should focus on populations of people with AUD who also report high levels of stress.
C Dots Show Powerful Tumor Killing Effect
Nanoparticles known as Cornell dots, or C dots, have shown great promise as a therapeutic tool in the detection and treatment of cancer.
Faecal Bacteria Linked to Body Fat
Researchers at King’s College London have found a new link between the diversity of bacteria in human poo – known as the human faecal microbiome - and levels of abdominal body fat.
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!