PMID- 22949667
OWN - NLM
STAT- MEDLINE
DCOM- 20121210
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 38
DP  - 2012 Sep 18
TI  - Conditional ablation of brain-derived neurotrophic factor-TrkB signaling impairs 
      striatal neuron development.
PG  - 15491-6
AB  - Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are 
      associated with the physiology of the striatum and the loss of its normal 
      functioning under pathological conditions. The role of BDNF and its downstream 
      signaling in regulating the development of the striatum has not been fully 
      investigated, however. Here we report that ablation of Bdnf in both the cortex 
      and substantia nigra depletes BDNF in the striatum, and leads to impaired 
      striatal development, severe motor deficits, and postnatal lethality. 
      Furthermore, striatal-specific ablation of TrkB, the gene encoding the 
      high-affinity receptor for BDNF, is sufficient to elicit an array of striatal 
      developmental abnormalities, including decreased anatomical volume, smaller 
      neuronal nucleus size, loss of dendritic spines, reduced enkephalin expression, 
      diminished nigral dopaminergic projections, and severe deficits in striatal 
      dopamine signaling through DARPP32. In addition, TrkB ablation in striatal 
      neurons elicits a non-cell-autonomous reduction of tyrosine hydroxylase protein 
      level in the axonal projections of substantia nigral dopaminergic neurons. Thus, 
      our results establish an essential function for TrkB in regulating the 
      development of striatal neurons.
FAU - Li, Yun
AU  - Li Y
AD  - Department of Developmental Biology and Kent Waldrep Center for Basic Research on 
      Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, 
      Dallas, TX 75390, USA.
FAU - Yui, Daishi
AU  - Yui D
FAU - Luikart, Bryan W
AU  - Luikart BW
FAU - McKay, Renee M
AU  - McKay RM
FAU - Li, Yanjiao
AU  - Li Y
FAU - Rubenstein, John L
AU  - Rubenstein JL
FAU - Parada, Luis F
AU  - Parada LF
LA  - eng
GR  - P50 MH066172/MH/NIMH NIH HHS/United States
GR  - R37 NS033199/NS/NINDS NIH HHS/United States
GR  - 7P50MH066172-07/MH/NIMH NIH HHS/United States
GR  - R37NS033199/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 - 20120904
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Axons/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Corpus Striatum/*metabolism
MH  - *Gene Expression Regulation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Neurons/*metabolism
MH  - Receptor, trkB/*metabolism
MH  - *Signal Transduction
MH  - Substantia Nigra/metabolism
MH  - Tyrosine 3-Monooxygenase/metabolism
PMC - PMC3458400
COIS- The authors declare no conflict of interest.
EDAT- 2012/09/06 06:00
MHDA- 2012/12/12 06:00
PMCR- 2013/03/18
CRDT- 2012/09/06 06:00
PHST- 2012/09/06 06:00 [entrez]
PHST- 2012/09/06 06:00 [pubmed]
PHST- 2012/12/12 06:00 [medline]
PHST- 2013/03/18 00:00 [pmc-release]
AID - 1212899109 [pii]
AID - 201212899 [pii]
AID - 10.1073/pnas.1212899109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15491-6. doi: 
      10.1073/pnas.1212899109. Epub 2012 Sep 4.