Navigation Links
The mysterious GRIN3A and the cause of schizophrenia
Date:3/14/2013

Philadelphia, PA, March 14, 2013 Since the 1960s, psychiatrists have been hunting for substances made by the body that might accumulate in abnormally high levels to produce the symptoms associated with schizophrenia. In particular, there was a search for chemicals that might be related to the hallucinogens phencyclidine (PCP) or lysergic acid diethylamide (LSD), which could explain the emergence of psychotic symptoms in schizophrenia. This "auto-intoxication" hypothesis led investigators on a wild goose chase where substances, including the "Pink Spot" and the "Frohman Factor", were isolated from people with schizophrenia and implicated in their illness, but these findings were later discredited.

The mysterious GRIN3A is a new version of the hunt for an intrinsic mechanism that produces schizophrenia-like symptoms. GRIN3A is a gene that codes for the GluN3A subunit of the N-methyl-D-aspartate-type (NMDA) receptor, a target for the neurotransmitter glutamate in the brain. Functional NMDA receptors usually have two GluN1 subunits and two GluN2 subunits. The ability of glutamate to activate these receptors is blocked by PCP and the anesthetic/hallucinogen, ketamine. When the GluN3A subunit is incorporated, it prevents the NMDA receptor from being activated by glutamate, almost as if the receptor had been blocked by PCP.

It is unclear why the brain needs this mechanism for normal brain development and function, hence the mystery surrounding GRIN3A. One piece of evidence supporting a link between GluN3A and schizophrenia is the finding that GluN3A levels are elevated in the post-mortem brain tissue from people who had been diagnosed with schizophrenia.

In this issue of Biological Psychiatry, Japanese researchers led by Dr. Takeo Yoshikawa provide new support for this hypothesis by implicating variation in GRIN3A in the heritable risk for schizophrenia.

Schizophrenia is thought to have a substantial genetic background which is, to some extent, population-specific. Genome-wide searches have revealed many common genomic variants with weak effects, but the remaining "missing heritability" is largely unknown. Scientists theorize that it may be partly explained by rare variants with large effect.

To identify genetic variants with larger effect sizes, Yoshikawa and his colleagues examined genetic data from several Asian populations. They identified a rare variant in GRIN3A with study-wide significance.

"This discovery is important, because the 'NMDA receptor hypothesis' for schizophrenia is a common disease model," said Yoshikawa. "We propose a novel point of therapeutic intervention in the NMDA receptor signaling system for schizophrenia."

Dr. John Krystal, Editor of Biological Psychiatry, commented, "The notion that a genetic trait that acts like PCP in the brain produces schizophrenia is a very attractive but over-simplistic hypothesis. It is that the biology of schizophrenia is much more complicated than this single factor. Nonetheless, perhaps this study of GRIN3A brings us another step closer to understanding glutamate abnormalities in schizophrenia."


'/>"/>

Contact: Rhiannon Bugno
Biol.Psych@utsouthwestern.edu
214-648-0880
Elsevier
Source:Eurekalert

Related biology news :

1. Researchers id queens, mysterious disease syndrome as key factors in bee colony deaths
2. Synchrotron infrared unveils a mysterious microbial community
3. Nunavuts mysterious ancient life could return by 2100
4. Mysterious snake disease decoded
5. Gene discovery set to help with mysterious paralysis of childhood
6. Life cycles of mysterious Namibian grassland fairy circles characterized
7. Low-cost nano-biosensor to detect foodborne pathogen that causes listeriosis
8. NASA pinpoints causes of 2011 Arctic ozone hole
9. Long-suspected cause of blindness from eye disease disproved
10. Protein abundant in cancerous cells causes DNA supercoiling
11. Why a hereditary anemia is caused by genetic mutation in mechanically sensitive ion channel
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/2/2016)... Calif. , Feb. 2, 2016  Based ... market, Frost & Sullivan recognizes US-based Intelligent Retinal ... Frost & Sullivan Award for New Product Innovation. ... in North America , is ... the rapidly growing diabetic retinopathy market. The IRIS ...
(Date:1/27/2016)... , Jan. 27, 2016  Rite Track, Inc. a ... West Chester, Ohio announced today ... service staff, based in Austin, Texas ... ability to provide modifications, installations and technical support offerings ... CEO of PLUS, commented, "PLUS has provided world class ...
(Date:1/21/2016)... --> ... report "Emotion Detection and Recognition Market by Technology (Bio-Sensors, NLP, ... Voice Recognition and Others), Services, Application Areas, End ... published by MarketsandMarkets, the global Emotion Detection and ... Billion by 2020, at a CAGR of 31.9%, ...
Breaking Biology News(10 mins):
(Date:2/10/2016)... ... February 10, 2016 , ... Global Stem Cells ... with Singapore-based Global Stem Cells Network (GSCN) and its affiliate Global Medical ... the latest adipose and bone marrow therapies. , Through the new collaboration, ...
(Date:2/9/2016)... ... February 08, 2016 , ... Date ... S. Blumberg Institute at the Pennsylvania Biotechnology Center of Bucks County, 3805 Old ... Commonwealth Medical College (TCMC) will hold an open house for participants to learn ...
(Date:2/9/2016)... Angeles, CA (PRWEB) , ... February 09, 2016 ... ... and strategic changes over the years and Open Access publishing is one of ... , With its 700+ open access journals and 3000+ International ...
(Date:2/9/2016)... , February 9, 2016 Three-Year Initiative ... Children to Take Part in Life-Changing Camp ... initiative designed to positively affect the lives of children born with ... --> SHPG ) is announcing a new initiative designed ... as well as the future of rare disease care. --> ...
Breaking Biology Technology: