Researchers Complete Picture of How Brain Mechanism Linked to Depression, Schizophrenia Functions

Erkan Karakas, Ph.D. - Brain and behavior research expert on depression
Erkan Karakas, Ph.D.

Newly published research by a former NARSAD Young Investigator Grantee provides an unprecedented view of a key brain receptor whose malfunction is implicated in depression, schizophrenia, Alzheimer’s and Parkinson’s diseases.

The receptor―one of many kinds of portals that sit on the surface of cells and enable them to interact with their surroundings―is called an NMDA (N-methyl, D-aspartate) receptor. It is found in abundance throughout the brain, on neurons that handle “excitatory” signals that facilitate nerve transmissions from cell to cell. Understanding how the NMDA receptor function is compromised in many disorders and diseases has been a longstanding and unsolved challenge for neuroscientists.

Erkan Karakas, Ph.D. (recipient of a 2009 NARSAD Young Investigator Grant) has worked with Associate Professor Hiro Furukawa, Ph.D., at Cold Spring Harbor Laboratory for several years to more fully flesh out how the NMDA receptor functions. Not until now, however, has the team succeeded in assembling a view of the receptor in its “full-length” form.

“To understand how the whole complex functions, you have to see it all together, fully assembled,” Drs. Karakas and Furukawa explain. After painstaking years of work, they finally solved the complete puzzle, and their results were published in Science on May 30th. Most important, this work reveals how the extracellular portion of NMDA receptors directly controls what is called the “ion channel.” Ion channels allow charged atoms to flow through the outside and inside of cells. This new insight about the NMDA receptor explains how it responds to excitatory signals from the neurotransmitter glutamate.

The researchers report that the new work fills in missing gaps of information, helping explain how NMDA receptors are distinct from what are called AMPA receptors, other common neuronal receptors that handle excitatory signals.

This new fully assembled view will enable further experiments to examine the function and dysfunction of NMDA receptors with new precision. The findings should also serve as an important blueprint for the development of novel treatments that can control NMDA receptors without affecting receptors in other kinds of cells, thus minimizing side effects.  

Read the paper abstract.

Article comments

I am very pleased to read about such research and the success of your work. I am hoping that such research will lead to better medicines with fewer side effects and a diagnostic tool such as a 100% effective blood test which will make it easier for the sufferer to understand and come to grips with the disorder. It is a real struggle for families when the sufferer doesn't accept and refuses treatment.

I am really pleased to read about your research and findings. I am hoping such research will lead to better medicines with fewer side effects. Also, a blood test great accuracy in diagnosing the illness will be really helpful for the sufferer to come to grips with the illness. It is very difficult for families struggling with a loved one who refuses the diagnosis and refuses treatment as well.

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Please note that researchers cannot give specific recommendations or advice about treatment; diagnosis and treatment are complex and highly individualized processes that require comprehensive face-to- face assessment. Please visit our "Ask an Expert" section to see a list of Q & A with NARSAD Grantees.
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