PMID- 30131699
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - EphB2 Deficiency Induces Depression-Like Behaviors and Memory Impairment: 
      Involvement of NMDA 2B Receptor Dependent Signaling.
PG  - 862
LID - 10.3389/fphar.2018.00862 [doi]
LID - 862
AB  - Receptor tyrosine kinase EphB2 mediates development of the neurogenic niche of 
      excitatory neurons, suggesting the possibility that its inactivation plays a role 
      in neuropsychiatric disorders including depression and memory impairment. While 
      N-methyl-D-aspartate (NMDA) receptor is involved in regulating memory formation 
      and neurogenesis in adult animal, it remains unclear how NMDA receptor subtypes 
      mediate depression and cognitive deficits caused by EphB2 loss. The present study 
      shows that EphB2 inactivation results in depression-like behaviors, memory 
      impairment and defects of adult hippocampal neurogenesis. Compared to wild-type 
      littermates, EphB2 KO mice exhibited depression-like behavior and deficits in 
      spatial memory and cognition in forced swimming, tail suspension, Morris water 
      maze, object recognition test and object location test. These behavioral 
      abnormalities were accompanied by substantial decreases in the number of BrdU+ 
      progenitor neurons, phosphorylation of cAMP-response element binding protein 
      (pCREB) and brain derived neurotrophic factor (BDNF), and increased NMDA receptor 
      2B (NR2B) expression. These molecular, cellular and behavioral alterations 
      induced by EphB2 inactivation were reversed by NR2B antagonist Ro25-6981, 
      suggesting that EphB2 functions to prevent the progression of depression-like 
      behavior and memory impairment by downregulating NR2B. Our findings highlight 
      that NR2B is responsible for EphB2-dependent behavioral and morphological 
      changes. EphB2 may thus be as an important candidate target for treating 
      psychiatric and cognitive disorders.
FAU - Zhen, Linlin
AU  - Zhen L
AD  - Department of Breast and Thyroid Surgery, The Affiliated Huai'an No. 1 People's 
      Hospital of Nanjing Medical University, Huai'an, China.
FAU - Shao, Tuo
AU  - Shao T
AD  - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
FAU - Luria, Victor
AU  - Luria V
AD  - Department of Systems Biology, Harvard University Medical School, Boston, MA, 
      United States.
FAU - Li, Gaowen
AU  - Li G
AD  - Department of Pharmacology, Ningbo College of Health Sciences, Ningbo, China.
FAU - Li, Zhi
AU  - Li Z
AD  - Department of Breast and Thyroid Surgery, The Affiliated Huai'an No. 1 People's 
      Hospital of Nanjing Medical University, Huai'an, China.
AD  - School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State 
      University of New York, Buffalo, NY, United States.
FAU - Xu, Ying
AU  - Xu Y
AD  - School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State 
      University of New York, Buffalo, NY, United States.
FAU - Zhao, Xin
AU  - Zhao X
AD  - Department of Pharmacology, School of Medical Science, Ningbo University, Ningbo, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20180807
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6090375
OTO - NOTNLM
OT  - EphB2
OT  - NMDA-2B receptor
OT  - NR2B antagonist Ro25-6981
OT  - cognition
OT  - depression
OT  - neurogenesis
EDAT- 2018/08/23 06:00
MHDA- 2018/08/23 06:01
PMCR- 2018/08/07
CRDT- 2018/08/23 06:00
PHST- 2018/05/26 00:00 [received]
PHST- 2018/07/17 00:00 [accepted]
PHST- 2018/08/23 06:00 [entrez]
PHST- 2018/08/23 06:00 [pubmed]
PHST- 2018/08/23 06:01 [medline]
PHST- 2018/08/07 00:00 [pmc-release]
AID - 10.3389/fphar.2018.00862 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Aug 7;9:862. doi: 10.3389/fphar.2018.00862. eCollection 
      2018.