PMID- 25979765
OWN - NLM
STAT- MEDLINE
DCOM- 20160302
LR  - 20171116
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 62
DP  - 2015 Oct 1
TI  - D-aspartate dysregulation in Ddo(-/-) mice modulates phencyclidine-induced gene 
      expression changes of postsynaptic density molecules in cortex and striatum.
PG  - 35-43
LID - S0278-5846(15)00093-7 [pii]
LID - 10.1016/j.pnpbp.2015.05.003 [doi]
AB  - N-methyl-D-aspartate receptor (NMDAR) hypofunction has been considered a key 
      alteration in schizophrenia pathophysiology. Thus, several strategies aimed at 
      enhancing glutamatergic transmission, included the introduction in therapy of 
      D-amino acids, such as D-serine and D-cycloserine augmentation, have been 
      proposed to counteract difficult-to-treat symptoms or treatment-resistant forms 
      of schizophrenia. Another D-amino acid, D-aspartate, has recently gained 
      increasing interest for its role in NMDAR activation and has been found reduced 
      in post-mortem cortex of schizophrenia patients. NMDAR is the core of the 
      postsynaptic density (PSD), a postsynaptic site involved in glutamate signaling 
      and responsive to antipsychotic treatment. In this study, we investigated 
      striatal and cortical gene expression of key PSD transcripts (i.e. Homer1a, 
      Homer1b/c, and PSD-95) in mice with persistently elevated brain 
      D-aspartate-levels, i.e. the D-aspartate-oxidase knockout mice (Ddo(-/-)). These 
      animal models were analyzed both in naive condition and after phencyclidine (PCP) 
      treatment. Naive Ddo(-/-) mice showed decreased Homer1a expression in the 
      prefrontal cortex, increased Homer1b/c expression in the striatum, and decreased 
      PSD-95 expression in the striatum and in the cortex. Acute PCP treatment 
      restored, and even potentiated, Homer1a expression in the prefrontal cortex of 
      mutant mice, while it had limited effects on the other genes. These results 
      suggest that persistently elevated D-aspartate, by enhancing NMDA transmission, 
      may cause complex adaptive mechanisms affecting Homer1a, which in turn may 
      explain the recently demonstrated protective effects of this D-amino acid against 
      PCP-induced behavioral alterations, such as ataxic behavior.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - de Bartolomeis, Andrea
AU  - de Bartolomeis A
AD  - Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, 
      Reproductive and Odontostomatological Sciences, University School of Medicine 
      Federico II, Naples, Italy. Electronic address: adebarto@unina.it.
FAU - Errico, Francesco
AU  - Errico F
AD  - CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Molecular Medicine 
      and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
FAU - Aceto, Giuseppe
AU  - Aceto G
AD  - CEINGE Biotecnologie Avanzate, Naples, Italy.
FAU - Tomasetti, Carmine
AU  - Tomasetti C
AD  - Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, 
      Reproductive and Odontostomatological Sciences, University School of Medicine 
      Federico II, Naples, Italy.
FAU - Usiello, Alessandro
AU  - Usiello A
AD  - CEINGE Biotecnologie Avanzate, Naples, Italy; Department of Environmental, 
      Biological and Pharmaceutical Sciences and Technologies, Second University of 
      Naples (SUN), Caserta, Italy.
FAU - Iasevoli, Felice
AU  - Iasevoli F
AD  - Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, 
      Reproductive and Odontostomatological Sciences, University School of Medicine 
      Federico II, Naples, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150512
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Carrier Proteins)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, mouse)
RN  - 0 (Homer Scaffolding Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (RNA, Messenger)
RN  - 4SR0Q8YD1X (D-Aspartic Acid)
RN  - EC 1.4.3.1 (D-Aspartate Oxidase)
RN  - EC 2.7.4.8 (Guanylate Kinases)
RN  - J1DOI7UV76 (Phencyclidine)
SB  - IM
MH  - Animals
MH  - Ataxia/chemically induced/metabolism
MH  - Carrier Proteins/metabolism
MH  - Cerebral Cortex/drug effects/*metabolism
MH  - Corpus Striatum/drug effects/*metabolism
MH  - D-Aspartate Oxidase/genetics/*metabolism
MH  - D-Aspartic Acid/*metabolism
MH  - Disks Large Homolog 4 Protein
MH  - Gene Expression/drug effects
MH  - Guanylate Kinases/metabolism
MH  - Homer Scaffolding Proteins
MH  - Membrane Proteins/metabolism
MH  - Mice, Knockout
MH  - Phencyclidine/*pharmacology
MH  - Psychotropic Drugs/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Random Allocation
OTO - NOTNLM
OT  - Homer
OT  - NMDAR
OT  - PSD-95
OT  - Psychosis
OT  - Treatment-resistant schizophrenia
EDAT- 2015/05/17 06:00
MHDA- 2016/03/05 06:00
CRDT- 2015/05/17 06:00
PHST- 2015/03/19 00:00 [received]
PHST- 2015/05/06 00:00 [revised]
PHST- 2015/05/06 00:00 [accepted]
PHST- 2015/05/17 06:00 [entrez]
PHST- 2015/05/17 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
AID - S0278-5846(15)00093-7 [pii]
AID - 10.1016/j.pnpbp.2015.05.003 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2015 Oct 1;62:35-43. doi: 
      10.1016/j.pnpbp.2015.05.003. Epub 2015 May 12.