PMID- 24746813
OWN - NLM
STAT- MEDLINE
DCOM- 20150105
LR  - 20231213
IS  - 2211-1247 (Electronic)
VI  - 7
IP  - 3
DP  - 2014 May 8
TI  - proBDNF negatively regulates neuronal remodeling, synaptic transmission, and 
      synaptic plasticity in hippocampus.
PG  - 796-806
LID - S2211-1247(14)00237-X [pii]
LID - 10.1016/j.celrep.2014.03.040 [doi]
AB  - Experience-dependent plasticity shapes postnatal development of neural circuits, 
      but the mechanisms that refine dendritic arbors, remodel spines, and impair 
      synaptic activity are poorly understood. Mature brain-derived neurotrophic factor 
      (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term 
      potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF, 
      which binds p75(NTR). In vitro, recombinant proBDNF modulates neuronal structure 
      and alters hippocampal long-term plasticity, but the actions of endogenously 
      expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant 
      probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates 
      hippocampal dendritic complexity and spine density through p75(NTR). Hippocampal 
      slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, 
      and enhanced long-term depression (LTD) in area CA1. These results suggest that 
      proBDNF acts in vivo as a biologically active factor that regulates hippocampal 
      structure, synaptic transmission, and plasticity, effects that are distinct from 
      those of mature BDNF.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Yang, Jianmin
AU  - Yang J
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Harte-Hargrove, Lauren C
AU  - Harte-Hargrove LC
AD  - The Nathan Kline Institute, Orangeburg, NY 10962, USA.
FAU - Siao, Chia-Jen
AU  - Siao CJ
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Marinic, Tina
AU  - Marinic T
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Clarke, Roshelle
AU  - Clarke R
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Ma, Qian
AU  - Ma Q
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Jing, Deqiang
AU  - Jing D
AD  - Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Lafrancois, John J
AU  - Lafrancois JJ
AD  - The Nathan Kline Institute, Orangeburg, NY 10962, USA.
FAU - Bath, Kevin G
AU  - Bath KG
AD  - Brown University, Providence, RI 02912, USA.
FAU - Mark, Willie
AU  - Mark W
AD  - Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
FAU - Ballon, Douglas
AU  - Ballon D
AD  - Department of Radiology, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Lee, Francis S
AU  - Lee FS
AD  - Department of Psychiatry, Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Scharfman, Helen E
AU  - Scharfman HE
AD  - The Nathan Kline Institute, Orangeburg, NY 10962, USA; New York University 
      Langone Medical Center, New York, NY 10016, USA. Electronic address: 
      hscharfman@nki.rfmh.org.
FAU - Hempstead, Barbara L
AU  - Hempstead BL
AD  - Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. 
      Electronic address: blhempst@med.cornell.edu.
LA  - eng
GR  - T32 MH067763/MH/NIMH NIH HHS/United States
GR  - P01 HD023315/HD/NICHD NIH HHS/United States
GR  - R01 NS064114/NS/NINDS NIH HHS/United States
GR  - R01 NS037562/NS/NINDS NIH HHS/United States
GR  - NS030627/NS/NINDS NIH HHS/United States
GR  - R01 NS052819/NS/NINDS NIH HHS/United States
GR  - T32 MH097763/MH/NIMH NIH HHS/United States
GR  - HD23315/HD/NICHD NIH HHS/United States
GR  - R01 NS030687/NS/NINDS NIH HHS/United States
GR  - NS37562/NS/NINDS NIH HHS/United States
GR  - NS064114/NS/NINDS NIH HHS/United States
GR  - NS052819/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140417
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Precursors)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Ngfr protein, mouse)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/chemistry/*genetics/metabolism
MH  - Cells, Cultured
MH  - Gene Knock-In Techniques
MH  - Hippocampus/anatomy & histology/cytology/*metabolism
MH  - Long-Term Synaptic Depression
MH  - Mice
MH  - Neuronal Plasticity/*physiology
MH  - Protein Binding
MH  - Protein Precursors/genetics/metabolism
MH  - Receptor, trkB/metabolism
MH  - Receptors, Nerve Growth Factor/chemistry/metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Synaptic Transmission/*physiology
PMC - PMC4118923
MID - NIHMS580404
EDAT- 2014/04/22 06:00
MHDA- 2015/01/06 06:00
PMCR- 2015/05/08
CRDT- 2014/04/22 06:00
PHST- 2013/08/10 00:00 [received]
PHST- 2014/01/30 00:00 [revised]
PHST- 2014/03/12 00:00 [accepted]
PHST- 2014/04/22 06:00 [entrez]
PHST- 2014/04/22 06:00 [pubmed]
PHST- 2015/01/06 06:00 [medline]
PHST- 2015/05/08 00:00 [pmc-release]
AID - S2211-1247(14)00237-X [pii]
AID - 10.1016/j.celrep.2014.03.040 [doi]
PST - ppublish
SO  - Cell Rep. 2014 May 8;7(3):796-806. doi: 10.1016/j.celrep.2014.03.040. Epub 2014 
      Apr 17.