Understanding schizophrenia: Researchers uncover new underlying mechanism

March 30, 2011 By Matet Nabres, University of Toronto

(PhysOrg.com) -- A new way of thinking about the fundamental pathobiology of schizophrenia could one day lead to improved therapeutic approaches to treating this disorder. Researchers at the University of Toronto, the Hospital for Sick Children (SickKids) and Tufts University School of Medicine have linked proteins and genes that are implicated in schizophrenia in a novel way. The study is published in the March 27 advance online edition of Nature Medicine.

Schizophrenia is a disorder that affects one per cent of Canadians and 24 million people worldwide. A team of researchers led by Professor Michael Salter of physiology and a senior scientists at SickKids identified a in the brain that may contribute to the neurobiological basis of .

“This is a paradigm shift in the way that we view the neural mechanisms of schizophrenia,” said Salter. “With our discovery we have brought together in a new way pieces of the schizophrenia puzzle. We hope that the understanding we have put together will lead to new forms of treatment that are more effective than the ones that are currently available.”

The scientists studied in mice two partner proteins, NRG1 and ErbB4, and the effect they have on a key brain receptor known as the N-methyl D-aspartate glutamate receptor (NMDAR). While NRG1 and ErbB4 have been genetically implicated in schizophrenia, the new study finds an unexpected link to NMDARs.

The NMDAR is a major component of synapses - the highly specialized sites of communication between the brain’s billions of individual nerve cells - that is critical for many brain functions including learning and memory. Suppressed functioning of NMDARs was suspected in schizophrenia because drugs that block NMDARs cause the hallucinations and disordered thought that occur in schizophrenia.

It had been suspected that NRG1 and ErbB4 might suppress generally NMDAR function but the present study found this was not the case. Rather, the researchers discovered that NRG1 and ErbB4 work together through inhibiting another , Src. The link to NMDARs is that Src normally increases NMDAR function under circumstances when this is needed such as in learning and memory. The researchers found that by blocking Src, NRG1 and ErbB4 selectively prevented that critical boost in NMDAR function.

The researchers also studied the responses of nerve cells during brain activity that mimicked normal brain oscillations known as theta rhythm. Theta rhythm activity, which is critical for learning and memory, is impaired in individuals with schizophrenia. The researchers determined that by acting through Src, NRG1 and ErbB4 greatly reduced the nerve cell responses to theta rhythm activity.

The findings suggest new approaches to schizophrenia treatment by reversing the effects of NRG1 and ErbB4 through enhancing the Src boost of NMDARs. “The tricky part is that all of these proteins are involved in other functions of the body; we can’t randomly enhance or inhibit them as this would lead to side effects,” Salter said. “The key will be to develop clever ways to target the proteins in the context of the synapse.”

Explore further: Pay attention – how the brain performs a background scan to help focus

Related Stories

Pay attention – how the brain performs a background scan to help focus

July 13, 2018
Research reveals that vision and brain circuits perform a regular background scan, making neurons available in case they are needed to focus on a task – enabling us to pay attention.

Eye movements reveal rhythm of memory formation

July 31, 2013
(Medical Xpress)—Quick eye movements, called saccades, that enable us to scan a visual scene appear to act as a metronome for pushing information about that scene into memory.

Surprise communication found between brain regions involved in infant motor control

May 4, 2017
A newborn's brain is abuzz with activity. Day and night, it's processing signals from all over the body, from recognizing the wriggles of the child's own fingers and toes to the sound of mommy's or daddy's voice.

Where 'where it's at' is at in the brain: Study in rats identifies region that associates objects and space

December 5, 2012
Conventional wisdom in brain research says that you just used your hippocampus to answer that question, but that might not be the whole story. The context of place depends on not just how you got there, but also the things ...

Memory and Alzheimer's: Towards a better comprehension of the dynamic mechanisms

August 31, 2014
A study just published in the prestigious Nature Neuroscience journal by, Sylvain Williams, PhD, and his team, of the Research Centre of the Douglas Mental Health University Institute and McGill University, opens the door ...

It don't mean a thing if the brain ain't got that swing

July 27, 2015
Like Duke Ellington's 1931 jazz standard, the human brain improvises while its rhythm section keeps up a steady beat. But when it comes to taking on intellectually challenging tasks, groups of neurons tune in to one another ...

Recommended for you

Team develops new way to grow blood vessels

August 17, 2018
Formation of new blood vessels, a process also known as angiogenesis, is one of the major clinical challenges in wound healing and tissue implants. To address this issue, researchers from Texas A&M University have developed ...

New imaging technique can spot tuberculosis infection in an hour

August 16, 2018
Guided by glowing bacteria, researchers have devised an imaging technique that can diagnose live tuberculosis in an hour and help monitor the efficacy of treatments. That's particularly critical because many TB strains have ...

Obesity, infertility and oxidative stress in mouse egg cells

August 16, 2018
Excessive body fat is associated with negative effects on female fertility and pregnancy. In mice, maternal obesity impairs proper development of egg precursor cells called oocytes. In a recent paper published in Molecular ...

Research shows it's possible to reverse damage caused by aging cells

August 15, 2018
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.

This matrix delivers healing stem cells to injured elderly muscles

August 15, 2018
A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method ...

Male tobacco smokers have brain-wide reduction of CB1 receptors

August 15, 2018
Chronic, frequent tobacco smokers have a decreased number of cannabinoid CB1 receptors, the "pot receptor", when compared with non-smokers, reports a study in Biological Psychiatry.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

JOHNSPEAKS
not rated yet Mar 30, 2011
Since when does the scientific community care about side effects? The mental health industry for the last hundred years has been experimenting with human beings similar to the Nazi experiments of world war II? How can you call this science when you use experimental antipsychotic drugs that have horrendous side effects? How can you use medical procedures that use inhuman experimentation such as -Deep Brain Stimulation- and -Electroshock Therapy- and -Deep Sleep Therapy- and -Adversion Therapy- and forms of -Lobotomy- etc.?
The Germans under Dr.Joseph Mengela were more humane than todays research scientists at least he gave the children candy before he experimented on them? You research scientist give a lifetime pain and suffering and false hope and then to end their suffering the clients have to use -Suicide- themselves to end their suffering? The Germans were more humane because they killed their lab rats quickly they did not want human beings to suffer?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.