Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
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 3,000+ 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

Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
A Patient’s Budding Cortex — In A Dish?
Networking neurons thrive in 3-D human “organoid”
Friday, May 29, 2015
Drugs that Activate Brain Stem Cells May Reverse Multiple Sclerosis
NIH-funded study identifies over-the-counter compounds that may replace damaged cells.
Tuesday, April 21, 2015
Stem Cell Transplants May Halt Progression of Multiple Sclerosis
NIH-funded study yields encouraging early results.
Tuesday, December 30, 2014
Scientists Sniff Out Unexpected Role for Stem Cells in the Brain
NIH scientists find that restocking new cells in the brain’s center for smell maintains crucial circuitry.
Saturday, October 11, 2014
Early Treatment Benefits Infants with Severe Combined Immunodeficiency
NIH-funded study identifies factors contributing to successful stem cell transplants.
Friday, August 01, 2014
Stem Cells Form Light-Sensitive 3-D Retinal Tissue
Researchers induced human stem cells to create a 3-D retina structure that responds to light. The finding may aid the study of eye diseases and could eventually lead to new therapies.
Tuesday, June 24, 2014
Stem Cell Therapy Rebuilds Heart Muscle in Primates
Human embryonic stem cells used to regenerate damaged primate hearts.
Tuesday, May 13, 2014
Too Much Protein May Kill Brain Cells As Parkinson’s Progresses
NIH-funded study on key Parkinson’s gene finds a possible new target for monitoring the disease.
Friday, April 11, 2014
NeuroBioBank Gives Researchers One-Stop Access to Post-Mortem Brains
The NIH is shifting from a limited funding role to coordinating a Web-based resource for sharing post-mortem brain tissue, a move which is expected to expedite research on brain disorders.
Tuesday, December 03, 2013
Gene-Silencing Study Finds New Targets for Parkinson’s Disease
NIH study sheds light on treatment of related disorders.
Monday, November 25, 2013
Epigenetic Clock Marks Age of Human Tissues and Cells
The age of many human tissues and cells is reflected in chemical changes to DNA. The finding provides insights for cancer, aging, and stem cell research.
Tuesday, November 05, 2013
NIH Scientists Pursue New Therapies to Improve Rare Disease Drug Development
Projects selected for potential to treat specific rare diseases.
Friday, September 13, 2013
Stem Cells Discovered in Deadly Parasitic Flatworms
The study was described in Nature on February 28, 2013.
Friday, March 15, 2013
New Type of Pluripotent Cell Discovered In Adult Breast Tissue
Human body carries personalized “patch kit," Say UCSF scientists.
Tuesday, March 05, 2013
Scientific News
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.
Heart Defect Prediction Technology Could Lead to Earlier, More Informed Treatment
Experimental method uses genetics-guided biomechanics, patient-specific stem cells.
Immune Cells Remember Their First Meal
Scientists at the University of Bristol have identified the trigger for immune cells' inflammatory response – a discovery that may pave the way for new treatments for many human diseases.
Cancer Cells Coordinate to Form Roving Clusters
Rice University scientists identify ‘smoking gun’ in metastasis of hybrid cells.
Bio-Mimicry Method For Preparing & Labeling Stem Cells Developed
Method allows researchers to prepare mesenchymal stem cells and monitor them using MRI.
Transcription Factor Isoforms Implicated in Colon Diseases
UC Riverside study explains how distribution of two forms of a transcription factor in the colon influence risk of disease.
New Bio-Glass Could Make it Possible to Re-Grow or Replace Cartilage
Researchers at Imperial College London have developed a material that can mimic cartilage and potentially encourage it to re-grow.
Stem Cell Advance Could Be Key Step Toward Treating Deadly Blood Diseases
UCLA scientists get closer to creating blood stem cells in the lab.
Harnessing Engineered Slippery Surfaces For Tissue Repair
A new method could facilitate the transfer of intact regenerating cell sheets from the culture dish to damaged tissues in patients.
Brazilian Zika Virus Strain Causes Birth Defects in Experimental Models
First direct experimental proof of causal effect, researchers say.
SELECTBIO

SELECTBIO Market Reports
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
3,000+ 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!