Tuesday, March 29, 2011

Understanding schizophrenia: researchers uncover new underlying mechanism


A March 28th media release from The Hospital for Sick Children:
TORONTO – 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 Hospital for Sick Children (SickKids), the University of Toronto 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 Dr. Michael Salter [pictured], SickKids Senior Scientist and Professor of Physiology at the University of Toronto, identified a biochemical pathway in the brain that may contribute to the neurobiological basis of schizophrenia.

“This is a paradigm shift in the way that we view the neural mechanisms of schizophrenia,” says Salter, Head of the Program in Neurosciences and Mental Health at SickKids Research Institute. “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 think, 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 protein, 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,” says Salter. “The key will be to develop clever ways to target the proteins in the context of the synapse.”

This study is funded by supported by the Canadian Institutes of Health Research, the Deafness Research Foundation, Howard Hughes Medical Institute and SickKids Foundation.


About The Hospital for Sick Children

The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally. Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision of Healthier Children. A Better World.™ For more information, please visit www.sickkids.ca.

About SickKids Research & Learning Tower

SickKids Research & Learning Tower will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs. The Tower will physically connect SickKids science, discovery and learning activities to its clinical operations. Designed by award-winning architects Diamond + Schmitt Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Tower will create an architectural landmark as the eastern gateway to Toronto’s Discovery District. SickKids Research & Learning Tower is funded by a grant from the Canada Foundation for Innovation and community support for the ongoing fundraising campaign. For more information, please visit www.buildsickkids.com.

For more information, please contact:

Matet Nebres
Manager, Media Relations
Communications and Public Affairs
The Hospital for Sick Children
Phone: 416-813-6380
Fax: 416-813-5328
email: matet.nebres@sickkids.ca

Suzanne Gold
Communications Specialist - Media Relations
Communications and Public Affairs
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
Fax: 416-813-5328
email: suzanne.gold@sickkids.ca

Photo credit

No comments: