Navigation Links
Schizophrenia Complicates With Altered Receptor Activity

When analyzing the neuronal receptor activity in the postmortem brain tissue from patients with schizophrenia, researchers at the University of Pennsylvania //School of Medicine, in collaboration with scientists at the City University of New York, have found a striking dysregulation in its function. A high level of erbB4 receptor activity and reduced NMDA receptor activity were identified when the receptors in the prefrontal cortex of schizophrenic patient were stimulated. Thus found a link between 2 receptor groups, that regulates a mechanism for decreased NMDA receptor function usually seen in schizophrenic patients.

Schizophrenia, a mental disorder afflicting approximately one percent of the world population, is characterized by a variety of symptoms such as: hallucinations, paranoia, disorganized behavior and the inability to experience pleasure. Previous studies of the brains of patients with schizophrenia suggest altered function in the prefrontal cortex, the brain's organizational center for cognitive function, personality expression, and behavioral control. International, large-scale genetic studies of patients with schizophrenia have pointed researchers to a gene called neuregulin 1 (NRG1), which appears to play a role in determining one's susceptibility to the disease.

Chang-Gyu Hahn, M.D., Ph.D., Assistant Professor of Psychiatry, Steven Arnold, M.D., Associate Professor of Psychiatry and Neurology, and Raquel Gur, M.D., Ph.D., Professor of Psychiatry, and colleagues at Penn, in collaboration with Hoau-Yan Wang, Ph.D., at The City University of New York, took an approach to use NRG1 protein to activate its neuronal receptor, erbB4, to measure the molecular response in postmortem brain tissue.

The binding of NRG1 to erbB4 stimulates neuronal receptor activity by adding phosphate molecules to the site of the receptor. The activation of erbB4, in turn, kicks off a cascade of molecular events within the neuron. When compari ng the initial steps of neurochemical activity in postmortem brain tissue of mentally healthy patients to those with schizophrenia, the researchers discovered that NRG1-erbB4 activity was significantly greater in the brains of patients with schizophrenia.

Hahn and colleagues also studied a second neuron receptor called NMDA, which receives input from the neurotransmitter glutamate. Previous studies at other labs have demonstrated the relationship between erbB4 and NMDA receptor activity and have led researchers to believe that enhanced activity of erbB4 receptors results in a decrease in NMDA receptor activity.

Low levels of NMDA receptor activity are believed to contribute to symptoms of schizophrenia. By stimulating NMDA receptors with glutamate, and measuring the subsequent changes in phosphorylation at the receptor, Penn scientists were able to track an impairment in NMDA receptor activation in the postmortem brain tissue from patients with schizophrenia.

‘The fact that our studies of the brains of patients with schizophrenia demonstrate both erbB4 receptor overactivity as well as NMDA underactivity suggests the existence of a relationship between these two receptor groups,’ explains Hahn. ‘Altered NRG1-erbB4 signaling may contribute to NMDA receptor hypofunction in schizophrenia.’ This finding is the first to display NMDA receptor hypofunction in the brains of patients with schizophrenia.

ErbB4 and NMDA receptors are located at the post-synaptic junction, or the chemical receiving end of the neuron. Both, erbB4 and NMDA receptors, are bound to scaffolding proteins called post-synaptic density (PSD), which can bridge receptor groups together and enhance their interactions.

‘PSD proteins can act like a raft in the ocean,’ explains Hahn. ‘Just as holding onto a raft increases one's chance of survival, by binding onto PSD proteins, NMDA and erbB4 receptors can enhance their activity.’

Hahn hypot hesizes that schizophrenia may be, in part, caused by the convergence of multiple factors (both genetic and epigenetic) at the PSD, which, in turn, alters the interaction of the molecules in the cellular environment, resulting in the symptoms of schizophrenia. In a continued attempt to understand the differences between the brains of mentally healthy patients and those with schizophrenia, future studies by the research team at Penn will focus on identifying differences in interactive dynamics of proteins in the PSD.

The postmortem brain stimulation method, established in this study, breaks out of the boundaries of previous research using postmortem brain tissue. Postmortem studies have historically focused on snapshot analyses of the brain at the time of death. This new method allows investigation of functional responses of brain tissue to stimulation. ‘Our hope is that this study will shift our postmortem methodologies from limited comparative studies to a more experimental approach,’ explains Arnold. ‘This will allow us to tease apart the molecular complexities that contribute to mental illnesses such as schizophrenia.’

(Source: Erekalert)
'"/>




Related medicine news :

1. Sex exploitation connected to Schizophrenia
2. Schizophrenia detected early
3. Gene glitches connecting pot with Schizophrenia
4. An insight about Schizophrenia
5. Risk Of Schizophrenia due to Gene Variation
6. Factors That Might Increase The Risk Of Schizophrenia
7. Identifying The Risks Of Developing Schizophrenia
8. Dads Age Found To Affect The Childs Risk for Schizophrenia
9. Famine May Be A Cause For Schizophrenia
10. Schizophrenia Gets A New Diagnostic Tool
11. Gene Activity connected to Schizophrenia
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/30/2016)... ... April 30, 2016 , ... Create an abstract ... can distort and manipulate three-dimensional shapes with ease all within Apple Motion ... lines, polygons, polygon texture animation, opacity texture animation, overall shape texture displacement, twist, ...
(Date:4/30/2016)... ... April 30, 2016 , ... Dr. ... CEO of EMED, today signed a multifaceted agreement which will allow for the ... Caribbean University Department of Natural and Applied Sciences, Allied Health and Nursing will ...
(Date:4/29/2016)... , ... April 30, 2016 , ... ... of patented products, announces the Pick Up Springboard, an automotive invention that improves ... Truck Manufacturing industry is worth $162 billion," says Scott Cooper, CEO and Creative ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... Accreditation Council for Graduate Medical Education (ACGME) that it has received accreditation for ... first accreditation of three residency programs that Memorial is currently pursuing, including Pediatrics ...
(Date:4/29/2016)... ... April 29, 2016 , ... ... of our nation’s productivity, stability, even security. Most importantly, employees are the single ... Then why are American workers so unhappy? , Just under half of American ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... 27, 2016 Global  urinalysis ... billion by 2022, according to a new report ... (Logo: http://photos.prnewswire.com/prnh/20150105/723757 ) , ... efficiency and accuracy delivered by the new generation ... novel urinalysis instruments and consumables. For instance, the ...
(Date:4/27/2016)... -- At the Sachs CEO forum in ... 2 clinical study of its lead drug candidate, STR001, ... (CI) surgery. This large, placebo-controlled, double-blind, phase 2 study ... and France . STR001 is ... of surgery. "Despite advances in cochlear implant technology, a ...
(Date:4/26/2016)... , April 26, 2016 Hill-Rom Holdings, Inc. ... a management presentation at the Deutsche Bank 41 st ... 2:50 p.m. EDT. You are invited to listen ... http://ir.hill-rom.com/events.cfm or access it directly at http://edge.media-server.com/m/p/mr4uxgas . ... hour after conclusion of the live event and accessible at ...
Breaking Medicine Technology: