PMID- 25043764
OWN - NLM
STAT- MEDLINE
DCOM- 20150519
LR  - 20211021
IS  - 1096-9861 (Electronic)
IS  - 0021-9967 (Print)
IS  - 0021-9967 (Linking)
VI  - 522
IP  - 17
DP  - 2014 Dec 1
TI  - Brain-derived neurotrophic factor but not vesicular zinc promotes TrkB activation 
      within mossy fibers of mouse hippocampus in vivo.
PG  - 3885-99
LID - 10.1002/cne.23647 [doi]
AB  - The neurotrophin receptor, TrkB receptor tyrosine kinase, is critical to central 
      nervous system (CNS) function in health and disease. Elucidating the ligands 
      mediating TrkB activation in vivo will provide insights into its diverse roles in 
      the CNS. The canonical ligand for TrkB is brain-derived neurotrophic factor 
      (BDNF). A diversity of stimuli also can activate TrkB in the absence of BDNF, a 
      mechanism termed transactivation. Zinc, a divalent cation packaged in synaptic 
      vesicles along with glutamate in axons of mammalian cortical neurons, can 
      transactivate TrkB in neurons and heterologous cells in vitro. Yet the 
      contributions of BDNF and zinc to TrkB activation in vivo are unknown. To address 
      these questions, we conducted immunohistochemical (IHC) studies of the 
      hippocampal mossy fiber axons and boutons using an antibody selective for pY816 
      of TrkB, a surrogate measure of TrkB activation. We found that conditional 
      deletion of BDNF resulted in a reduction of pY816 in axons and synaptic boutons 
      of hippocampal mossy fibers, thereby implicating BDNF in activation of TrkB in 
      vivo. Unexpectedly, pY816 immunoreactivity was increased in axons but not 
      synaptic boutons of mossy fibers in ZnT3 knockout mice that lack vesicular zinc. 
      Marked increases of BDNF content were evident within the hippocampus of ZnT3 
      knockout mice and genetic elimination of BDNF reduced pY816 immunoreactivity in 
      these mice, implicating BDNF in enhanced TrkB activation mediated by vesicular 
      zinc depletion. These findings support the conclusion that BDNF but not vesicular 
      zinc activates TrkB in hippocampal mossy fiber axons under physiological 
      conditions.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Helgager, Jeffrey
AU  - Helgager J
AD  - Department of Neurobiology, Duke University Medical Center, Durham, NC, 27710.
FAU - Huang, Yang Zhong
AU  - Huang YZ
FAU - Mcnamara, James O
AU  - Mcnamara JO
LA  - eng
GR  - R01 NS056217/NS/NINDS NIH HHS/United States
GR  - R01 NS065960/NS/NINDS NIH HHS/United States
GR  - T32 GM008441/GM/NIGMS NIH HHS/United States
GR  - NS065960/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140825
PL  - United States
TA  - J Comp Neurol
JT  - The Journal of comparative neurology
JID - 0406041
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Slc30a3 protein, mouse)
RN  - 0 (Synapsins)
RN  - 0 (tau-1 monoclonal antibody)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cation Transport Proteins
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation/genetics
MH  - Hippocampus/*cytology
MH  - Membrane Proteins/genetics/*metabolism
MH  - Membrane Transport Proteins
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microscopy, Confocal
MH  - Mossy Fibers, Hippocampal/*metabolism
MH  - Mutation/genetics
MH  - Receptor, trkB/chemistry/*metabolism
MH  - Synapsins/metabolism
PMC - PMC4167967
MID - NIHMS611869
OTO - NOTNLM
OT  - TrkB
OT  - hippocampus
OT  - immunohistochemistry
OT  - mossy fiber
OT  - neurotrophin
OT  - zinc
COIS- CONFLICT OF INTEREST STATEMENT The authors state no conflict of interest.
EDAT- 2014/07/22 06:00
MHDA- 2015/05/20 06:00
PMCR- 2015/12/01
CRDT- 2014/07/22 06:00
PHST- 2014/02/25 00:00 [received]
PHST- 2014/06/29 00:00 [revised]
PHST- 2014/06/30 00:00 [accepted]
PHST- 2014/07/22 06:00 [entrez]
PHST- 2014/07/22 06:00 [pubmed]
PHST- 2015/05/20 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1002/cne.23647 [doi]
PST - ppublish
SO  - J Comp Neurol. 2014 Dec 1;522(17):3885-99. doi: 10.1002/cne.23647. Epub 2014 Aug 
      25.