PMID- 23843530
OWN - NLM
STAT- MEDLINE
DCOM- 20130920
LR  - 20211021
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 28
DP  - 2013 Jul 10
TI  - Distinct roles for somatically and dendritically synthesized brain-derived 
      neurotrophic factor in morphogenesis of dendritic spines.
PG  - 11618-32
LID - 10.1523/JNEUROSCI.0012-13.2013 [doi]
AB  - Dendritic spines undergo the processes of formation, maturation, and pruning 
      during development. Molecular mechanisms controlling spine maturation and pruning 
      remain largely unknown. The gene for brain-derived neurotrophic factor (BDNF) 
      produces two pools of mRNA, with either a short or long 3' untranslated region 
      (3' UTR). Our previous results show that short 3' UTR Bdnf mRNA is restricted to 
      cell bodies, whereas long 3' UTR Bdnf mRNA is also trafficked to dendrites for 
      local translation. Mutant mice lacking long 3' UTR Bdnf mRNA display normal 
      spines at 3 weeks of age, but thinner and denser spines in adults compared to 
      wild-type littermates. These observations suggest that BDNF translated from long 
      3' UTR Bdnf mRNA, likely in dendrites, is required for spine maturation and 
      pruning. In this study, using rat hippocampal neuronal cultures, we found that 
      knocking down long 3' UTR Bdnf mRNA blocked spine head enlargement and spine 
      elimination, whereas overexpressing long 3' UTR Bdnf mRNA had the opposite 
      effect. The effect of long 3' UTR Bdnf mRNA on spine head enlargement and spine 
      elimination was diminished by a human single-nucleotide polymorphism (SNP, 
      rs712442) in its 3' UTR that inhibited dendritic localization of Bdnf mRNA. 
      Furthermore, we found that overexpression of either Bdnf mRNA increased spine 
      density at earlier time points. Spine morphological alterations were associated 
      with corresponding changes in density, size, and function of synapses. These 
      results indicate that somatically synthesized BDNF promotes spine formation, 
      whereas dendritically synthesized BDNF is a key regulator of spine head growth 
      and spine pruning.
FAU - Orefice, Lauren L
AU  - Orefice LL
AD  - Department of Pharmacology and Physiology, Georgetown University Medical Center, 
      Washington, DC 20057, USA.
FAU - Waterhouse, Emily G
AU  - Waterhouse EG
FAU - Partridge, John G
AU  - Partridge JG
FAU - Lalchandani, Rupa R
AU  - Lalchandani RR
FAU - Vicini, Stefano
AU  - Vicini S
FAU - Xu, Baoji
AU  - Xu B
LA  - eng
GR  - R01 NS050596/NS/NINDS NIH HHS/United States
GR  - F30DK084717/DK/NIDDK NIH HHS/United States
GR  - R01 NS073930/NS/NINDS NIH HHS/United States
GR  - F30 DK084717/DK/NIDDK NIH HHS/United States
GR  - F31 NS074840/NS/NINDS NIH HHS/United States
GR  - NS074840/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cells, Cultured
MH  - Dendrites/metabolism
MH  - Dendritic Spines/*genetics
MH  - Female
MH  - HEK293 Cells
MH  - Hippocampus/*embryology/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Morphogenesis/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC3724547
EDAT- 2013/07/12 06:00
MHDA- 2013/09/21 06:00
PMCR- 2014/01/10
CRDT- 2013/07/12 06:00
PHST- 2013/07/12 06:00 [entrez]
PHST- 2013/07/12 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
PHST- 2014/01/10 00:00 [pmc-release]
AID - 33/28/11618 [pii]
AID - 0012-13 [pii]
AID - 10.1523/JNEUROSCI.0012-13.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Jul 10;33(28):11618-32. doi: 10.1523/JNEUROSCI.0012-13.2013.