PMID- 33907230
OWN - NLM
STAT- MEDLINE
DCOM- 20211027
LR  - 20220830
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Apr 27
TI  - Altered neural oscillations and behavior in a genetic mouse model of NMDA 
      receptor hypofunction.
PG  - 9031
LID - 10.1038/s41598-021-88428-9 [doi]
LID - 9031
AB  - Abnormalities in electroencephalographic (EEG) biomarkers occur in patients with 
      schizophrenia and those clinically at high risk for transition to psychosis and 
      are associated with cognitive impairment. Converging evidence suggests 
      N-methyl-D-aspartate receptor (NMDAR) hypofunction plays a central role in the 
      pathophysiology of schizophrenia and likely contributes to biomarker impairments. 
      Thus, characterizing these biomarkers is of significant interest for early 
      diagnosis of schizophrenia and development of novel treatments. We utilized in 
      vivo EEG recordings and behavioral analyses to perform a battery of 
      electrophysiological biomarkers in an established model of chronic NMDAR 
      hypofunction, serine racemase knockout (SRKO) mice, and their wild-type 
      littermates. SRKO mice displayed impairments in investigation-elicited gamma 
      power that corresponded with reduced short-term social recognition and enhanced 
      background (pre-investigation) gamma activity. Additionally, SRKO mice exhibited 
      sensory gating impairments in both evoked-gamma power and event-related potential 
      amplitude. However, other biomarkers including the auditory steady-state 
      response, sleep spindles, and state-specific power spectral density were 
      generally neurotypical. In conclusion, SRKO mice demonstrate how chronic NMDAR 
      hypofunction contributes to deficits in certain translationally-relevant EEG 
      biomarkers altered in schizophrenia. Importantly, our gamma band findings suggest 
      an aberrant signal-to-noise ratio impairing cognition that occurs with NMDAR 
      hypofunction, potentially tied to impaired task-dependent alteration in 
      functional connectivity.
FAU - Aguilar, David D
AU  - Aguilar DD
AD  - VA Boston Healthcare System, West Roxbury, MA, USA. 
      David_Aguilar@hms.harvard.edu.
AD  - Department of Psychiatry, Harvard Medical School, Boston, MA, USA. 
      David_Aguilar@hms.harvard.edu.
FAU - Radzik, Leana K
AU  - Radzik LK
AD  - Department of Neuroscience, Stonehill College, Easton, MA, USA.
FAU - Schiffino, Felipe L
AU  - Schiffino FL
AD  - VA Boston Healthcare System, West Roxbury, MA, USA.
AD  - Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
FAU - Folorunso, Oluwarotimi O
AU  - Folorunso OO
AD  - Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
AD  - Translational Psychiatry Laboratory, McLean Hospital, Belmont, MA, USA.
FAU - Zielinski, Mark R
AU  - Zielinski MR
AD  - VA Boston Healthcare System, West Roxbury, MA, USA.
AD  - Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
FAU - Coyle, Joseph T
AU  - Coyle JT
AD  - Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
AD  - Laboratory of Psychiatric and Molecular Neuroscience, McLean Hospital, Belmont, 
      MA, USA.
FAU - Balu, Darrick T
AU  - Balu DT
AD  - Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
AD  - Translational Psychiatry Laboratory, McLean Hospital, Belmont, MA, USA.
FAU - McNally, James M
AU  - McNally JM
AD  - VA Boston Healthcare System, West Roxbury, MA, USA.
AD  - Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
LA  - eng
GR  - IK2 BX002823/BX/BLRD VA/United States
GR  - 2019021/United States-Israel Binational Science Foundation/
GR  - R01NS098740-02/NS/NINDS NIH HHS/United States
GR  - IK2 BX002130/BX/BLRD VA/United States
GR  - R03 AG063201/AG/NIA NIH HHS/United States
GR  - I01 BX004500/BX/BLRD VA/United States
GR  - F32 MH119838/MH/NIMH NIH HHS/United States
GR  - R01 NS098740/NS/NINDS NIH HHS/United States
GR  - T32 MH016259/MH/NIMH NIH HHS/United States
GR  - F32MH119838/MH/NIMH NIH HHS/United States
GR  - T32MH016259/MH/NIMH NIH HHS/United States
GR  - 1R03AG063201-01/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210427
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 5.1.- (Racemases and Epimerases)
RN  - EC 5.1.1.16 (serine racemase)
SB  - IM
MH  - Animals
MH  - Biomarkers
MH  - Disease Models, Animal
MH  - Electroencephalography
MH  - Female
MH  - Gamma Rhythm
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Racemases and Epimerases/genetics/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Schizophrenia/diagnosis/*metabolism/physiopathology
MH  - Sensory Gating
MH  - Social Behavior
PMC - PMC8079688
COIS- All authors except JTC and DTB declare no competing financial interests in 
      relation to the work described. JTC reports holding a patent on D-serine to treat 
      serious mental disorder that is owned by Massachusetts General Hospital but could 
      yield royalties, and a patent on an AI-based EEG method to predict psychotropic 
      drug response. DTB served as a consultant for LifeSci Capital and received 
      research support from Takeda Pharmaceuticals.
EDAT- 2021/04/29 06:00
MHDA- 2021/10/28 06:00
PMCR- 2021/04/27
CRDT- 2021/04/28 06:00
PHST- 2021/03/05 00:00 [received]
PHST- 2021/04/09 00:00 [accepted]
PHST- 2021/04/28 06:00 [entrez]
PHST- 2021/04/29 06:00 [pubmed]
PHST- 2021/10/28 06:00 [medline]
PHST- 2021/04/27 00:00 [pmc-release]
AID - 10.1038/s41598-021-88428-9 [pii]
AID - 88428 [pii]
AID - 10.1038/s41598-021-88428-9 [doi]
PST - epublish
SO  - Sci Rep. 2021 Apr 27;11(1):9031. doi: 10.1038/s41598-021-88428-9.