XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
 Latest Research
 Cancer
 Psychiatry
  Depression
  Neuropsychiatry
  Personality Disorders
  Bulimia
  Anxiety
  Substance Abuse
  Suicide
  CFS
  Psychoses
   Bipolar Disorder
   Schizophrenia
  Child Psychiatry
  Learning-Disabilities
  Psychology
  Forensic Psychiatry
  Mood Disorders
  Sleep Disorders
  Peri-Natal Psychiatry
  Psychotherapy
  Anorexia Nervosa
 Genetics
 Surgery
 Aging
 Ophthalmology
 Gynaecology
 Neurosciences
 Pharmacology
 Cardiology
 Obstetrics
 Infectious Diseases
 Respiratory Medicine
 Pathology
 Endocrinology
 Immunology
 Nephrology
 Gastroenterology
 Biotechnology
 Radiology
 Dermatology
 Microbiology
 Haematology
 Dental
 ENT
 Environment
 Embryology
 Orthopedics
 Metabolism
 Anaethesia
 Paediatrics
 Public Health
 Urology
 Musculoskeletal
 Clinical Trials
 Physiology
 Biochemistry
 Cytology
 Traumatology
 Rheumatology
 
 Medical News
 Health
 Opinion
 Healthcare
 Professionals
 Launch
 Awards & Prizes
 
 Careers
 Medical
 Nursing
 Dental
 
 Special Topics
 Euthanasia
 Ethics
 Evolution
 Odd Medical News
 Feature
 
 World News
 Tsunami
 Epidemics
 Climate
 Business
Search

Last Updated: Aug 19th, 2006 - 22:18:38

Schizophrenia Channel
subscribe to Schizophrenia newsletter

Latest Research : Psychiatry : Psychoses : Schizophrenia

   DISCUSS   |   EMAIL   |   PRINT
NMDA receptor hypofunction demonstrated in schizophrenia
Jun 19, 2006, 01:26, Reviewed by: Dr. Ankush Vidyarthi

"Altered NRG1-erbB4 signaling may contribute to NMDA receptor hypofunction in schizophrenia."

 
Researchers at the University of Pennsylvania School of Medicine, in collaboration with scientists at the City University of New York, have identified a striking dysregulation in neuronal receptor activity in the postmortem brain tissue from patients with schizophrenia. By stimulating receptors in the prefrontal cortex, the research team tracked heightened levels of erbB4 receptor activity, as well as decreased NMDA receptor activity in the tissue from patients with schizophrenia. Additionally, they were able to identify a relationship between these two receptor groups, suggesting a mechanism for decreased NMDA receptor function that has long been suspected in schizophrenia.

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 comparing 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 hypothesizes 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."
 

- The researchers report their findings in this week's advanced online issue of Nature Medicine.
 

www.uphs.upenn.edu

 
Subscribe to Schizophrenia Newsletter
E-mail Address:

 

Study co-authors are Dan-Sung Cho, Konrad Talbot, Wade H. Berrettini, Joshua Kamins, Karin E. Borgmann-Winter and Steven J. Siegel, all from Penn, as well as Kalindi Bakshi, from The City University of New York Medical School and Robert J. Gallop, from West Chester University. This research was funded in part by the National Institutes of Health and the Stanley Research Foundation.

PENN Medicine is a $2.9 billion enterprise dedicated to the related missions of medical education, biomedical research and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #3 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System includes three hospitals [Hospital of the University of Pennsylvania, which is consistently ranked one of the nation's few "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center]; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.


Related Schizophrenia News

Study aims to identify schizophrenics at risk for type 2 diabetes
Effects of ketamine mimic only some of the symptoms of schizophrenia
Association between famine and schizophrenia may yield clues about genetic basis
Neuropeptide S (NPS) may help in treating schizophrenia
Neuropeptide S (NPS) may help in treating schizophrenia
NMDA receptor hypofunction demonstrated in schizophrenia
Altered NRG1-erbB4 signaling may contribute to NMDA receptor hypofunction in schizophrenia
Transcription factor Elk-1's role in neurodegeneration and schizophrenia
Schizophrenia limits one's ability to perceive body language
Hospitalized schizophrenics are at a higher risk for developing medical/surgical complications


For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us