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:6/3/2016)... LONDON , June 3, 2016 /PRNewswire/ ... Transport Management) von Nepal ... ,Angebot und Lieferung hochsicherer geprägter Kennzeichen, einschließlich ... weltweit führend in der Produktion und Implementierung ... an der Ausschreibung im Januar teilgenommen, aber ...
(Date:6/2/2016)... June 2, 2016   The Weather Company , an ... Ads, an industry-first capability in which consumers will be able ... to ask questions via voice or text and receive relevant ... Marketers have long sought an advertising solution ... can be personal, relevant and valuable; and can scale across ...
(Date:6/1/2016)... 2016 Favorable Government Initiatives Coupled ... Criminal Identification to Boost Global Biometrics System Market Through ... Research report, " Global Biometrics Market By Type, ... Opportunities, 2011 - 2021", the global biometrics market is ... account of growing security concerns across various end use ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... ... launch of the Supplyframe Design Lab . Located in Pasadena, Calif., the ... future of how hardware projects are designed, built and brought to market. , ...
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case report published today ... a patient who developed lymphedema after being treated for breast cancer benefitted from an ... paradigm for dealing with this debilitating, frequent side effect of cancer treatment. ...
(Date:6/23/2016)... Calif. , June 23, 2016  Blueprint Bio, ... biological discoveries to the medical community, has closed its ... Matthew Nunez . "We have received ... with the capital we need to meet our current ... essentially provide us the runway to complete validation on ...
(Date:6/23/2016)... On Wednesday, June 22, 2016, the ... the Dow Jones Industrial Average edged 0.27% lower to finish ... 0.17%. Stock-Callers.com has initiated coverage on the following equities: Infinity ... NKTR ), Aralez Pharmaceuticals Inc. (NASDAQ: ... ). Learn more about these stocks by accessing their free ...
Breaking Biology Technology: