PMID- 16815329
OWN - NLM
STAT- MEDLINE
DCOM- 20060831
LR  - 20150813
IS  - 0896-6273 (Print)
IS  - 0896-6273 (Linking)
VI  - 51
IP  - 1
DP  - 2006 Jul 6
TI  - In vivo restoration of physiological levels of truncated TrkB.T1 receptor rescues 
      neuronal cell death in a trisomic mouse model.
PG  - 21-8
AB  - Imbalances in neurotrophins or their high-affinity Trk receptors have long been 
      reported in neurodegenerative diseases. However, a molecular link between these 
      gene products and neuronal cell death has not been established. In the trisomy 16 
      (Ts16) mouse there is increased apoptosis in the cortex, and hippocampal neurons 
      undergo accelerated cell death that cannot be rescued by administration of 
      brain-derived neurotrophic factor (BDNF). Ts16 neurons have normal levels of the 
      TrkB tyrosine kinase receptor but an upregulation of the TrkB.T1 truncated 
      receptor isoform. Here we show that restoration of the physiological level of the 
      TrkB.T1 receptor by gene targeting rescues Ts16 cortical cell and hippocampal 
      neuronal death. Moreover, it corrects resting Ca2+ levels and restores 
      BDNF-induced intracellular signaling mediated by full-length TrkB in Ts16 
      hippocampal neurons. These data provide a direct link between neuronal cell death 
      and abnormalities in Trk neurotrophin receptor levels.
FAU - Dorsey, Susan G
AU  - Dorsey SG
AD  - Neural Development Group, Mouse Cancer Genetics Program, Center for Cancer 
      Research, National Cancer Institute, Frederick, Maryland 21702, USA. 
      sdorsey@son.umaryland.edu
FAU - Renn, Cynthia L
AU  - Renn CL
FAU - Carim-Todd, Laura
AU  - Carim-Todd L
FAU - Barrick, Colleen A
AU  - Barrick CA
FAU - Bambrick, Linda
AU  - Bambrick L
FAU - Krueger, Bruce K
AU  - Krueger BK
FAU - Ward, Christopher W
AU  - Ward CW
FAU - Tessarollo, Lino
AU  - Tessarollo L
LA  - eng
GR  - K01-AR02177/AR/NIAMS NIH HHS/United States
GR  - K22NR00174/NR/NINR NIH HHS/United States
GR  - R01NS40492/NS/NINDS NIH HHS/United States
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PL  - United States
TA  - Neuron
JT  - Neuron
JID - 8809320
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Isoforms)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - SY7Q814VUP (Calcium)
SB  - IM
CIN - Neuron. 2006 Jul 6;51(1):1-3. PMID: 16815323
MH  - Animals
MH  - Apoptosis/genetics
MH  - Brain/cytology/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/metabolism
MH  - Disease Models, Animal
MH  - Down-Regulation/genetics
MH  - Gene Targeting/methods
MH  - Hippocampus/cytology/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Neurologic Mutants
MH  - Molecular Weight
MH  - Nerve Degeneration/*genetics/metabolism/physiopathology
MH  - Neurons/cytology/*metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - Receptor, trkB/*genetics
MH  - Recovery of Function/genetics
MH  - Signal Transduction/genetics
MH  - Trisomy/*genetics/physiopathology
EDAT- 2006/07/04 09:00
MHDA- 2006/09/01 09:00
CRDT- 2006/07/04 09:00
PHST- 2005/05/26 00:00 [received]
PHST- 2006/01/13 00:00 [revised]
PHST- 2006/06/09 00:00 [accepted]
PHST- 2006/07/04 09:00 [pubmed]
PHST- 2006/09/01 09:00 [medline]
PHST- 2006/07/04 09:00 [entrez]
AID - S0896-6273(06)00462-4 [pii]
AID - 10.1016/j.neuron.2006.06.009 [doi]
PST - ppublish
SO  - Neuron. 2006 Jul 6;51(1):21-8. doi: 10.1016/j.neuron.2006.06.009.