PMID- 29563866
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 12
DP  - 2018
TI  - The 3' UTRs of Brain-Derived Neurotrophic Factor Transcripts Differentially 
      Regulate the Dendritic Arbor.
PG  - 60
LID - 10.3389/fncel.2018.00060 [doi]
LID - 60
AB  - The patterning of dendrites is regulated by many factors, such as brain-derived 
      neurotrophic factor (BDNF), which our laboratory has previously shown alters the 
      dendritic arbor uniquely depending on the mode of extracellular application. In 
      the current work, we examine how BDNF affects dendritogenesis in hippocampal 
      neurons when it is overexpressed intracellularly by transcripts previously 
      reported to be transported to distinct cellular compartments. The BDNF gene is 
      processed at two different polyadenylation sites, leading to mRNA transcription 
      with two different length 3' untranslated regions (UTRs), and therefore, 
      different mRNA localization preferences. We found that overexpression of BDNF 
      mRNA with or without 3' UTRs significantly alters dendritic branching compared to 
      branching in control neurons as analyzed by Sholl distribution curves. 
      Unexpectedly, we found that the overexpression of the shorter BDNF mRNA (reported 
      to be preferentially targeted to the cell body) results in similar changes to 
      Sholl curves compared to overexpression of the longer BDNF mRNA (reported to be 
      preferentially targeted to both the cell body and dendrites). We also 
      investigated whether the BDNF receptor TrkB mediates these changes and found that 
      inhibiting TrkB blocks increases in Sholl curves, although at different distances 
      depending on the transcript's UTR. Finally, although it is not found in nature, 
      we also examined the effects of overexpressing BDNF mRNA with the unique portion 
      of the longer 3' UTR since it was previously shown to be necessary for dendritic 
      targeting of mRNA. We found that its overexpression increases Sholl curves at 
      distances close to the cell body and that these changes also depend on TrkB 
      activity. This work illustrates how the mRNA spatial code affects how BDNF alters 
      local dendritogenesis and how TrkB may mediate these effects. Finally, our 
      findings emphasize the importance of intracellular transport of BDNF mRNAs in the 
      regulation of dendrite morphology.
FAU - O'Neill, Kate M
AU  - O'Neill KM
AD  - Department of Cell Biology and Neuroscience, Rutgers University, The State 
      University of New Jersey, Piscataway, NJ, United States.
AD  - Graduate Program in Biomedical Engineering, Rutgers University, The State 
      University of New Jersey, Piscataway, NJ, United States.
FAU - Donohue, Katherine E
AU  - Donohue KE
AD  - Department of Cell Biology and Neuroscience, Rutgers University, The State 
      University of New Jersey, Piscataway, NJ, United States.
FAU - Omelchenko, Anton
AU  - Omelchenko A
AD  - Department of Cell Biology and Neuroscience, Rutgers University, The State 
      University of New Jersey, Piscataway, NJ, United States.
AD  - Graduate Program in Neuroscience, Rutgers University, The State University of New 
      Jersey, Piscataway, NJ, United States.
FAU - Firestein, Bonnie L
AU  - Firestein BL
AD  - Department of Cell Biology and Neuroscience, Rutgers University, The State 
      University of New Jersey, Piscataway, NJ, United States.
AD  - Biomedical Engineering Graduate Faculty, Rutgers University, The State University 
      of New Jersey, Piscataway, NJ, United States.
AD  - Neuroscience Graduate Faculty, Rutgers University, The State University of New 
      Jersey, Piscataway, NJ, United States.
LA  - eng
GR  - T32 GM008339/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20180307
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC5845904
OTO - NOTNLM
OT  - 3' UTR
OT  - Sholl analysis
OT  - brain-derived neurotrophic factor
OT  - dendrite arborization
OT  - hippocampal neurons
OT  - mRNA
EDAT- 2018/03/23 06:00
MHDA- 2018/03/23 06:01
PMCR- 2018/01/01
CRDT- 2018/03/23 06:00
PHST- 2017/11/20 00:00 [received]
PHST- 2018/02/19 00:00 [accepted]
PHST- 2018/03/23 06:00 [entrez]
PHST- 2018/03/23 06:00 [pubmed]
PHST- 2018/03/23 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2018.00060 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2018 Mar 7;12:60. doi: 10.3389/fncel.2018.00060. eCollection 
      2018.