PMID- 38086803
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20231216
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 14
IP  - 1
DP  - 2023 Dec 12
TI  - D-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal 
      neurons in a neurodevelopmental mouse model for schizophrenia.
PG  - 8255
LID - 10.1038/s41467-023-43930-8 [doi]
LID - 8255
AB  - The hypothesis of N-methyl-D-aspartate receptor (NMDAR) dysfunction for cognitive 
      impairment in schizophrenia constitutes the theoretical basis for the 
      translational application of NMDAR co-agonist D-serine or its analogs. However, 
      the cellular mechanism underlying the therapeutic effect of D-serine remains 
      unclear. In this study, we utilize a mouse neurodevelopmental model for 
      schizophrenia that mimics prenatal pathogenesis and exhibits hypoexcitability of 
      parvalbumin-positive (PV) neurons, as well as PV-preferential NMDAR dysfunction. 
      We find that D-serine restores excitation/inhibition balance by reconstituting 
      both synaptic and intrinsic inhibitory control of cingulate pyramidal neurons 
      through facilitating PV excitability and activating small-conductance 
      Ca(2+)-activated K(+) (SK) channels in pyramidal neurons, respectively. Either 
      amplifying inhibitory drive via directly strengthening PV neuron activity or 
      inhibiting pyramidal excitability via activating SK channels is sufficient to 
      improve cognitive function in this model. These findings unveil a dual mechanism 
      for how D-serine improves cognitive function in this model.
CI  - (c) 2023. The Author(s).
FAU - Zhang, Xiao-Qin
AU  - Zhang XQ
AUID- ORCID: 0000-0003-0254-7598
AD  - Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua 
      Rd, Ningbo, Zhejiang, 315211, China.
FAU - Xu, Le
AU  - Xu L
AUID- ORCID: 0000-0002-9801-8764
AD  - Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua 
      Rd, Ningbo, Zhejiang, 315211, China.
FAU - Zhu, Xin-Yi
AU  - Zhu XY
AUID- ORCID: 0009-0006-8106-4277
AD  - Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua 
      Rd, Ningbo, Zhejiang, 315211, China.
FAU - Tang, Zi-Hang
AU  - Tang ZH
AD  - Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua 
      Rd, Ningbo, Zhejiang, 315211, China.
FAU - Dong, Yi-Bei
AU  - Dong YB
AD  - Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua 
      Rd, Ningbo, Zhejiang, 315211, China.
FAU - Yu, Zhi-Peng
AU  - Yu ZP
AD  - Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua 
      Rd, Ningbo, Zhejiang, 315211, China.
FAU - Shang, Qing
AU  - Shang Q
AUID- ORCID: 0000-0003-3868-2097
AD  - Department of Neurology, The First Affiliated Hospital of Ningbo University, 59 
      Liuting Street, Haishu District, Ningbo, Zhejiang, 315211, China.
FAU - Wang, Zheng-Chun
AU  - Wang ZC
AD  - Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua 
      Rd, Ningbo, Zhejiang, 315211, China.
FAU - Shen, Hao-Wei
AU  - Shen HW
AUID- ORCID: 0000-0002-2766-5139
AD  - Department of Pharmacology, School of Medicine, Ningbo University, 818 Fenghua 
      Rd, Ningbo, Zhejiang, 315211, China. shenhaowei@nbu.edu.cn.
LA  - eng
GR  - 32171017/National Natural Science Foundation of China (National Science 
      Foundation of China)/
GR  - 31571094/National Natural Science Foundation of China (National Science 
      Foundation of China)/
PT  - Journal Article
DEP - 20231212
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 452VLY9402 (Serine)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Pregnancy
MH  - Female
MH  - *Schizophrenia/drug therapy
MH  - Serine/pharmacology
MH  - Pyramidal Cells/physiology
MH  - Neurons/metabolism
MH  - Synaptic Transmission
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
PMC - PMC10716516
COIS- The authors declare no competing interests.
EDAT- 2023/12/13 00:41
MHDA- 2023/12/17 09:45
PMCR- 2023/12/12
CRDT- 2023/12/12 23:17
PHST- 2022/09/26 00:00 [received]
PHST- 2023/11/24 00:00 [accepted]
PHST- 2023/12/17 09:45 [medline]
PHST- 2023/12/13 00:41 [pubmed]
PHST- 2023/12/12 23:17 [entrez]
PHST- 2023/12/12 00:00 [pmc-release]
AID - 10.1038/s41467-023-43930-8 [pii]
AID - 43930 [pii]
AID - 10.1038/s41467-023-43930-8 [doi]
PST - epublish
SO  - Nat Commun. 2023 Dec 12;14(1):8255. doi: 10.1038/s41467-023-43930-8.