Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Repairing the brain

21.09.2015

Two genes unlock potential for treatment of schizophrenia

Research led by scientists from Duke-NUS Graduate Medical School Singapore (Duke-NUS) has linked the abnormal behaviour of two genes (BDNF and DTNBP1) to the underlying cause of schizophrenia. These findings have provided a new target for schizophrenia treatment.


This is an image of a cultured neuron with an added BDNF protein.

Credit: Duke-NUS Graduate Medical School Singapore

Schizophrenia is a devastating mental disorder that affects nearly 1% of the total human population. The dominant cause of the disorder lies in impaired brain development that eventually leads to imbalanced signals within the brain. This imbalance within the brain is thought to cause hallucinations and paranoia in people with schizophrenia.

"We wanted to understand the mechanism by which the brain circuit operates," explained senior author Assistant Professor Shawn Je, from the Neuroscience and Behavioural Disorders Programme at Duke-NUS. "In particular, we wanted to understand the ability of a specific type of cell in the brain, termed interneurons, to modulate brain network activity to maintain a balance in brain signalling."

Dr. Je and his team analysed signalling activity in neuronal cultures that either did not have the DTNBP1 gene or had lowered levels of the gene, because reduced DTNBP1 levels and genetic disruptions of DTNBP1 in mice resulted in schizophrenia-like behaviours. Using multiple model systems, they found that the low levels of DTNBP1 resulted in dysfunctional interneurons and over-activated neuronal network activity. Reducing levels of DTNBP1 also lowered the levels of the secreted protein molecule, BDNF.

BDNF was then shown to be one of the most important factors that regulate the development of a normal brain circuit. It plays an important role in the interneurons ability to connect to the brain. Interneurons receive BDNF via a transport system run by DTNBP1. This can be likened to the delivery of a parcel: DTNBP1 is the driver of the delivery van and without the driver, the parcel BDNF cannot be delivered to the required destination. Without BDNF, the abnormal circuit development and brain network activity observed in schizophrenia patients results.

Additionally, Dr. Je and his team also found that when BDNF levels were restored, brain development and activity were rescued and returned to more normal levels, despite the absence of DTNBP1.

While the two genes DTNBP1 and BDNF have been singled out as risk genes for schizophrenia in studies before, this is the first study to show that the two function together. Pinpointing the importance of the abnormal delivery of BDNF has shed considerable insight into how the brain network develops. It also presents possibilities for potential treatments for schizophrenia designed around enhancing BDNF levels.

In a follow-up study, Dr. Je plans to test if these findings are viable in an animal model. If proven successful, this could mean that correcting the imbalance within the brain circuits of schizophrenia patients may bring us closer to producing a treatment.

###

Study facts at a glance:

  • The study was published online in the journal Biological Psychiatry.
  • DTNBP1 and BDNF are two genes that increase the risk of schizophrenia.
  • Dr. Je's study is the first ever to show that DTNBP1 is required for proper trafficking of BDNF to its appropriate location within the brain circuit.
  • BDNF is required for the development and action of interneurons within the brain circuit that maintains signalling balance.
  • Results have shown that regulating BDNF levels can rescue the signalling imbalance observed in schizophrenia, providing new hope for a treatment.

 

Media Contact

Dharshini Subbiah
dharshini.subbiah@duke-nus.edu.sg
65-961-67532

 @dukenus

http://www.duke-nus.edu.sg 

Dharshini Subbiah | EurekAlert!

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>