PMID- 23543703
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130402
LR  - 20220321
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 7
DP  - 2013
TI  - NMDA hypofunction as a convergence point for progression and symptoms of 
      schizophrenia.
PG  - 31
LID - 10.3389/fncel.2013.00031 [doi]
LID - 31
AB  - Schizophrenia is a disabling mental illness that is now recognized as a 
      neurodevelopmental disorder. It is likely that genetic risk factors interact with 
      environmental perturbations to affect normal brain development and that this 
      altered trajectory results in a combination of positive, negative, and cognitive 
      symptoms. Although the exact pathophysiology of schizophrenia is unknown, the 
      N-methyl-D-aspartate receptor (NMDAR), a major glutamate receptor subtype, has 
      received great attention. Proper expression and regulation of NMDARs in the brain 
      is critical for learning and memory processes as well as cortical plasticity and 
      maturation. Evidence from both animal models and human studies implicates a 
      dysfunction of NMDARs both in disease progression and symptoms of schizophrenia. 
      Furthermore, mutations in many of the known genetic risk factors for 
      schizophrenia suggest that NMDAR hypofunction is a convergence point for 
      schizophrenia. In this review, we discuss how disrupted NMDAR function leads to 
      altered neurodevelopment that may contribute to the progression and development 
      of symptoms for schizophrenia, particularly cognitive deficits. We review the 
      shared signaling pathways among the schizophrenia susceptibility genes DISC1, 
      neuregulin1, and dysbindin, focusing on the AKT/GSK3beta pathway, and how their 
      mutations and interactions can lead to NMDAR dysfunction during development. 
      Additionally, we explore what open questions remain and suggest where 
      schizophrenia research needs to move in order to provide mechanistic insight into 
      the cause of NMDAR dysfunction, as well as generate possible new avenues for 
      therapeutic intervention.
FAU - Snyder, Melissa A
AU  - Snyder MA
AD  - Department of Neurobiology and Anatomy, Drexel University College of Medicine 
      Philadelphia, PA, USA.
FAU - Gao, Wen-Jun
AU  - Gao WJ
LA  - eng
GR  - R01 MH085666/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20130327
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC3608949
OTO - NOTNLM
OT  - NMDA receptors
OT  - gene
OT  - neurodevelopment
OT  - psychiatric disorders
OT  - schizophrenia
EDAT- 2013/04/02 06:00
MHDA- 2013/04/02 06:01
PMCR- 2013/01/01
CRDT- 2013/04/02 06:00
PHST- 2012/12/03 00:00 [received]
PHST- 2013/03/11 00:00 [accepted]
PHST- 2013/04/02 06:00 [entrez]
PHST- 2013/04/02 06:00 [pubmed]
PHST- 2013/04/02 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2013.00031 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2013 Mar 27;7:31. doi: 10.3389/fncel.2013.00031. eCollection 
      2013.