PMID- 29695955
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 11
DP  - 2018
TI  - GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role 
      of Hippocampal NR2B and DISC1.
PG  - 121
LID - 10.3389/fnmol.2018.00121 [doi]
LID - 121
AB  - Background: Evidence supports that the hypofunction of N-methyl-D-aspartate 
      receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) 
      contribute to the pathophysiology of schizophrenia. N-Methyl D-aspartate receptor 
      subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in 
      schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and 
      cognitive enhancer that does not induce psychotomimetic side effects. However, it 
      remains unclear whether NR2B plays a critical role in the GLYX-13-induced 
      alleviation of schizophrenia-like behaviors in mice. Methods: The effect of 
      GLYX-13 was tested by observing changes in locomotor activity, novel object 
      recognition ability, and prepulse inhibition (PPI) induced by dizocilpine (known 
      as MK-801) in mice. Lentivirus-mediated NR2B knockdown in the hippocampus was 
      assessed to confirm the role of NR2B in GLYX-13 pathophysiology, using Western 
      blots and immunohistochemistry. Results: The systemic administration of GLYX-13 
      (0.5 and 1 mg/kg, i.p.) ameliorates MK-801 (0.5 mg/kg, i.p.)-induced 
      hyperlocomotion, deficits in memory, and PPI in mice. Additionally, GLYX-13 
      normalized the MK-801-induced alterations in signaling molecules, including NR2B 
      and DISC1 in the hippocampus. Furthermore, we found that NR2B knockdown produced 
      memory and PPI deficits without any changes in locomotor activity. Notably, DISC1 
      levels significantly decreased by NR2B knockdown. However, the effective dose of 
      GLYX-13 did not alleviate the memory and PPI dysfunctions or downregulation of 
      DISC1 induced by NR2B knockdown. Conclusion: Our results suggest GLYX-13 as a 
      candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may 
      account for the molecular mechanisms of GLYX-13.
FAU - Zhou, Dongsheng
AU  - Zhou D
AD  - Ningbo Kangning Hospital, Ningbo, China.
AD  - Ningbo Key Laboratory of Behavioral Neuroscience, School of Medicine, Ningbo 
      University, Ningbo, China.
FAU - Lv, Dan
AU  - Lv D
AD  - Ningbo Key Laboratory of Behavioral Neuroscience, School of Medicine, Ningbo 
      University, Ningbo, China.
AD  - Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo 
      University, Ningbo, China.
AD  - Department of Physiology and Pharmacology, School of Medicine, Ningbo University, 
      Ningbo, China.
FAU - Wang, Zhen
AU  - Wang Z
AD  - Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, 
      Chinese Academy of Sciences, Shanghai, China.
FAU - Zhang, Yanhua
AU  - Zhang Y
AD  - Ningbo Key Laboratory of Behavioral Neuroscience, School of Medicine, Ningbo 
      University, Ningbo, China.
AD  - Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo 
      University, Ningbo, China.
AD  - Department of Physiology and Pharmacology, School of Medicine, Ningbo University, 
      Ningbo, China.
FAU - Chen, Zhongming
AU  - Chen Z
AD  - Ningbo Kangning Hospital, Ningbo, China.
FAU - Wang, Chuang
AU  - Wang C
AD  - Ningbo Key Laboratory of Behavioral Neuroscience, School of Medicine, Ningbo 
      University, Ningbo, China.
AD  - Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo 
      University, Ningbo, China.
AD  - Department of Physiology and Pharmacology, School of Medicine, Ningbo University, 
      Ningbo, China.
LA  - eng
PT  - Journal Article
DEP - 20180411
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
CIN - Front Mol Neurosci. 2018 Sep 05;11:315. PMID: 30233316
PMC - PMC5904356
OTO - NOTNLM
OT  - GLYX-13
OT  - N-methyl D-aspartate receptor subtype 2B
OT  - N-methyl-D-aspartate receptor
OT  - disrupted-in-schizophrenia 1
OT  - schizophrenia
EDAT- 2018/04/27 06:00
MHDA- 2018/04/27 06:01
PMCR- 2018/01/01
CRDT- 2018/04/27 06:00
PHST- 2017/12/03 00:00 [received]
PHST- 2018/03/28 00:00 [accepted]
PHST- 2018/04/27 06:00 [entrez]
PHST- 2018/04/27 06:00 [pubmed]
PHST- 2018/04/27 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2018.00121 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2018 Apr 11;11:121. doi: 10.3389/fnmol.2018.00121. 
      eCollection 2018.