PMID- 25461194
OWN - NLM
STAT- MEDLINE
DCOM- 20160829
LR  - 20151007
IS  - 1095-953X (Electronic)
IS  - 0969-9961 (Linking)
VI  - 73
DP  - 2015 Jan
TI  - Mice with subtle reduction of NMDA NR1 receptor subunit expression have a 
      selective decrease in mismatch negativity: Implications for schizophrenia 
      prodromal population.
PG  - 289-95
LID - S0969-9961(14)00303-9 [pii]
LID - 10.1016/j.nbd.2014.10.010 [doi]
AB  - Reductions in glutamate function are regarded as an important contributory factor 
      in schizophrenia. However, there is a paucity of animal models characterized by 
      developmental and sustained reductions in glutamate function. Pharmacological 
      models using NMDA antagonists have been widely used but these typically produce 
      only transient changes in behavior and brain function. Likewise, mice with 
      homozygous constitutive reductions in glutamate receptor expression show stable 
      brain and behavioral changes, but many of these phenotypes are more severe than 
      the human disease. The current study examines a variety of schizophrenia-related 
      EEG measures in mice with a heterozygous alteration of the NMDA receptor NR1 
      subunit gene (NR1) that is known to result in reduced NR1 receptor expression in 
      the homozygous mouse (NR1-/-). (NR1+/-) mice showed a 30% reduction in NR1 
      receptor expression and were reared after weaning in either group or isolated 
      conditions. Outcome measures include the response to paired white noise stimuli, 
      escalating inter-stimulus intervals (ISIs) and deviance-related mismatch 
      negativity (MMN). In contrast to what has been reported in (NR1-/-) mice and mice 
      treated with NMDA antagonists, (NR1+/-) mice showed no change on obligatory Event 
      Related Potential (ERP) measures including the murine P50 and N100 equivalents 
      (P20 and N40), or measures of baseline or evoked gamma power. Alternatively, 
      (NR1+/-) mice showed a marked reduction in response to a deviant auditory tone 
      during MMN task. Data suggest that EEG response to deviant, rather than static, 
      stimuli may be more sensitive for detecting subtle changes in glutamate function. 
      Deficits in these heterozygous NR1 knockdown mice are consistent with data 
      demonstrating MMN deficits among family members of schizophrenia patients and 
      among prodromal patients. Therefore, the current study suggests that (NR1+/-) 
      mice may be among the most sensitive models for increased vulnerability to 
      schizophrenia.
CI  - Copyright (c) 2015. Published by Elsevier Inc.
FAU - Featherstone, Robert E
AU  - Featherstone RE
AD  - Translational Neuroscience Program, Department of Psychiatry, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Shin, Rick
AU  - Shin R
AD  - Translational Psychiatry, CNS - Astellas Research Institute of America LLC, 
      Skokie, IL, USA.
FAU - Kogan, Jeffrey H
AU  - Kogan JH
AD  - Translational Psychiatry, CNS - Astellas Research Institute of America LLC, 
      Skokie, IL, USA.
FAU - Liang, Yuling
AU  - Liang Y
AD  - Translational Neuroscience Program, Department of Psychiatry, University of 
      Pennsylvania, Philadelphia, PA, USA.
FAU - Matsumoto, Mitsuyuki
AU  - Matsumoto M
AD  - Translational Psychiatry, CNS - Astellas Research Institute of America LLC, 
      Skokie, IL, USA.
FAU - Siegel, Steven J
AU  - Siegel SJ
AD  - Translational Neuroscience Program, Department of Psychiatry, University of 
      Pennsylvania, Philadelphia, PA, USA. Electronic address: siegels@upenn.edu.
LA  - eng
GR  - 5R01DA023210-02/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141022
PL  - United States
TA  - Neurobiol Dis
JT  - Neurobiology of disease
JID - 9500169
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Animals
MH  - Brain/*physiopathology
MH  - Disease Models, Animal
MH  - Evoked Potentials/*physiology
MH  - Gamma Rhythm/*physiology
MH  - Genetic Predisposition to Disease
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Prodromal Symptoms
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Schizophrenia/*physiopathology
MH  - *Social Isolation
OTO - NOTNLM
OT  - EEG
OT  - Mismatch negativity
OT  - Mouse
OT  - NMDA
OT  - Schizophrenia
EDAT- 2014/12/03 06:00
MHDA- 2016/08/30 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/04/17 00:00 [received]
PHST- 2014/10/06 00:00 [revised]
PHST- 2014/10/12 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2016/08/30 06:00 [medline]
AID - S0969-9961(14)00303-9 [pii]
AID - 10.1016/j.nbd.2014.10.010 [doi]
PST - ppublish
SO  - Neurobiol Dis. 2015 Jan;73:289-95. doi: 10.1016/j.nbd.2014.10.010. Epub 2014 Oct 
      22.