PMID- 38444127
OWN - NLM
STAT- MEDLINE
DCOM- 20240307
LR  - 20240307
IS  - 0371-0874 (Print)
IS  - 0371-0874 (Linking)
VI  - 76
IP  - 1
DP  - 2024 Feb 25
TI  - Inhibition of GluN2B-containing NMDA receptors in early life combined with social 
      stress in adulthood leads to alterations in prefrontal PNNs in mice.
PG  - 1-11
AB  - Perineuronal nets (PNNs) are specialized extracellular matrix (ECM) structures 
      present in the central nervous system (CNS) and have been identified as 
      significant regulators of developmental plasticity in the developing cortex. PNNs 
      are particularly enriched in the cortex surrounding parvalbumin-expressing 
      (PV(+)) cells. A growing body of evidence suggests that the abnormalities in 
      PV(+) neurons and PNNs are associated with various neurological disorders, 
      including schizophrenia, which is a neurodevelopmental defect disease. The 
      N-methyl-D-aspartate receptor (NMDAR) selective antagonist is frequently employed 
      to establish animal models of schizophrenia in laboratory settings. The crucial 
      involvement of GluN2B-containing NMDARs in the development of CNS has been 
      extensively established. However, the role of GluN2B in the pathophysiology of 
      schizophrenia has yet to be thoroughly investigated. The present study inhibited 
      GluN2B function through intraperitoneal infusion of the GluN2B selective 
      antagonist ifenprodil into juvenile mice aged 3-4 weeks, followed by the 
      administration of social stress when these mice reached 9 weeks of age. Then, 
      immunofluorescence staining was employed to examine the changes in the PNNs and 
      PV(+) cells, an acoustic startle and prepulse inhibition test was used to detect 
      activities of the PV(+) cells, and Western blot was used to quantify the protein 
      expression levels of GluN2A and GluN2B in the prefrontal cortex (PFC). The study 
      revealed that in the PFC of mice subjected to GluN2B antagonist treatment in 
      early life and social stress in adulthood, there was an increase in the number of 
      PV(+) cells wrapped by PNNs, and a decrease in the activation of PV(+) cells 
      during the prepulse inhibition test, which is an indicator of sensory gating 
      functions, as well as changes in the protein expression levels of GluN2A and 
      GluN2B, which resulted in an increase in the ratio of GluN2A to GluN2B. These 
      aberrations in the mice are comparable to those observed in animal models and 
      patients with schizophrenia. The findings suggest that even a transient 
      hypofunction of GluN2B in early life poses a significant risk for the emergence 
      of schizophrenia symptoms in adulthood.
FAU - Liang, Yi-Rui
AU  - Liang YR
AD  - State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
FAU - Zhang, Xue-Han
AU  - Zhang XH
AD  - State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain 
      Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China. 
      xuehanzhang@fudan.edu.cn.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Sheng Li Xue Bao
JT  - Sheng li xue bao : [Acta physiologica Sinica]
JID - 20730130R
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PNN protein, human)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (NR2B NMDA receptor)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Cell Adhesion Molecules
MH  - Central Nervous System
MH  - Cerebral Cortex
MH  - Extracellular Matrix
MH  - Nuclear Proteins
MH  - *Receptors, N-Methyl-D-Aspartate
MH  - *Stress, Psychological
EDAT- 2024/03/06 06:43
MHDA- 2024/03/07 06:43
CRDT- 2024/03/06 00:53
PHST- 2024/03/07 06:43 [medline]
PHST- 2024/03/06 06:43 [pubmed]
PHST- 2024/03/06 00:53 [entrez]
PST - ppublish
SO  - Sheng Li Xue Bao. 2024 Feb 25;76(1):1-11.