PMID- 32796766
OWN - NLM
STAT- MEDLINE
DCOM- 20210614
LR  - 20210614
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 10
IP  - 8
DP  - 2020 Aug 11
TI  - Multi-Scale Understanding of NMDA Receptor Function in Schizophrenia.
LID - 10.3390/biom10081172 [doi]
LID - 1172
AB  - Schizophrenia is a chronic and disabling psychiatric disorder characterized by 
      disturbances of thought, cognition, and behavior. Despite massive research 
      efforts to date, the etiology and pathophysiology of schizophrenia remain largely 
      unknown. The difficulty of brain research is largely a result of complex 
      interactions between contributory factors at different scales: susceptible gene 
      variants (molecular scale), synaptopathies (synaptic, dendritic, and cell 
      scales), and alterations in neuronal circuits (circuit scale), which together 
      result in behavioral manifestations (individual scale). It is likely that each 
      scale affects the others, from the microscale to the mesoscale to the macroscale, 
      and vice versa. Thus, to consider the intricate complexity of schizophrenia 
      across multiple layers, we introduce a multi-scale, hierarchical view of the 
      nature of this disorder, focusing especially on N-methyl-D-aspartate-type 
      glutamate receptors (NMDARs). The reason for placing emphasis on NMDAR is its 
      clinical relevance to schizophrenia, as well as its diverse functions in neurons, 
      including the robust supralinear synaptic integration provided by 
      N-methyl-D-aspartate-type glutamate (NMDA) spikes and the Ca(2+) permeability of 
      the NMDAR, which facilitates synaptic plasticity via various calcium-dependent 
      proteins. Here, we review recent evidence implicating NMDARs in the 
      pathophysiology of schizophrenia from the multi-scale perspective. We also 
      discuss recent advances from optical techniques, which provide a powerful tool 
      for uncovering the mechanisms of NMDAR synaptic pathology and their 
      relationships, with subsequent behavioral manifestations.
FAU - Hyun, Jo Soo
AU  - Hyun JS
AUID- ORCID: 0000-0002-1587-745X
AD  - Laboratory for Multi-scale Biological Psychiatry, Center for Brain Science, 
      RIKEN, 2-1 Hirosawa, Wako City, Saitama Prefecture 351-0106, Japan.
AD  - Department of Life Science and Medical Bioscience, School of Advanced Science and 
      Engineering, Waseda University, Tokyo 162-8480, Japan.
FAU - Inoue, Takafumi
AU  - Inoue T
AD  - Department of Life Science and Medical Bioscience, School of Advanced Science and 
      Engineering, Waseda University, Tokyo 162-8480, Japan.
FAU - Hayashi-Takagi, Akiko
AU  - Hayashi-Takagi A
AD  - Laboratory for Multi-scale Biological Psychiatry, Center for Brain Science, 
      RIKEN, 2-1 Hirosawa, Wako City, Saitama Prefecture 351-0106, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200811
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Humans
MH  - Neuronal Plasticity
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Schizophrenia/*metabolism
PMC - PMC7465114
OTO - NOTNLM
OT  - multi-scale
OT  - schizophrenia
OT  - synaptic optogenetics
OT  - synaptic pathology
COIS- The authors declare no conflict of interest.
EDAT- 2020/08/17 06:00
MHDA- 2021/06/16 06:00
PMCR- 2020/08/01
CRDT- 2020/08/16 06:00
PHST- 2020/05/20 00:00 [received]
PHST- 2020/08/06 00:00 [revised]
PHST- 2020/08/07 00:00 [accepted]
PHST- 2020/08/16 06:00 [entrez]
PHST- 2020/08/17 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - biom10081172 [pii]
AID - biomolecules-10-01172 [pii]
AID - 10.3390/biom10081172 [doi]
PST - epublish
SO  - Biomolecules. 2020 Aug 11;10(8):1172. doi: 10.3390/biom10081172.