Understanding schizophrenia: Researchers uncover new underlying mechanism

Mar 30, 2011 By Matet Nabres

(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: Scientists identify critical new protein complex involved in learning and memory

Related Stories

Recommended for you

LED exposure is not harmful to human dermal fibroblasts

13 hours ago

There was a time when no one thought about light bulbs—one blew, you screwed another one in. Nowadays, it's more complicated, as energy efficiency concerns have given rise to a slew of options, including ...

User comments : 1

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?

More news stories

Man among first in US to get 'bionic eye' (Update)

A degenerative eye disease slowly robbed Roger Pontz of his vision. Diagnosed with retinitis pigmentosa as a teenager, Pontz has been almost completely blind for years. Now, thanks to a high-tech procedure ...