PMID- 24991961
OWN - NLM
STAT- MEDLINE
DCOM- 20140902
LR  - 20211021
IS  - 1097-4199 (Electronic)
IS  - 0896-6273 (Print)
IS  - 0896-6273 (Linking)
VI  - 83
IP  - 1
DP  - 2014 Jul 2
TI  - Impaired TrkB receptor signaling underlies corticostriatal dysfunction in 
      Huntington's disease.
PG  - 178-88
LID - S0896-6273(14)00447-4 [pii]
LID - 10.1016/j.neuron.2014.05.032 [doi]
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. 
      The debilitating choreic movements that plague HD patients have been attributed 
      to striatal degeneration induced by the loss of cortically supplied brain-derived 
      neurotrophic factor (BDNF). Here, we show that in mouse models of early 
      symptomatic HD, BDNF delivery to the striatum and its activation of 
      tyrosine-related kinase B (TrkB) receptors were normal. However, in striatal 
      neurons responsible for movement suppression, TrkB receptors failed to properly 
      engage postsynaptic signaling mechanisms controlling the induction of 
      potentiation at corticostriatal synapses. Plasticity was rescued by inhibiting 
      p75 neurotrophin receptor (p75NTR) signaling or its downstream 
      target phosphatase-and-tensin-homolog-deleted-on-chromosome-10 (PTEN). Thus, 
      corticostriatal synaptic dysfunction early in HD is attributable to a correctable 
      defect in the response to BDNF, not its delivery.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Plotkin, Joshua L
AU  - Plotkin JL
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Day, Michelle
AU  - Day M
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Peterson, Jayms D
AU  - Peterson JD
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Xie, Zhong
AU  - Xie Z
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Kress, Geraldine J
AU  - Kress GJ
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Rafalovich, Igor
AU  - Rafalovich I
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Kondapalli, Jyothisri
AU  - Kondapalli J
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Gertler, Tracy S
AU  - Gertler TS
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Flajolet, Marc
AU  - Flajolet M
AD  - Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 
      New York, NY 10065, USA.
FAU - Greengard, Paul
AU  - Greengard P
AD  - Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 
      New York, NY 10065, USA.
FAU - Stavarache, Mihaela
AU  - Stavarache M
AD  - Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 
      10028, USA.
FAU - Kaplitt, Michael G
AU  - Kaplitt MG
AD  - Department of Neurological Surgery, Weill Cornell Medical College, New York, NY 
      10028, USA.
FAU - Rosinski, Jim
AU  - Rosinski J
AD  - CHDI Management/CHDI Foundation, Princeton, NJ 08540, USA.
FAU - Chan, C Savio
AU  - Chan CS
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA.
FAU - Surmeier, D James
AU  - Surmeier DJ
AD  - Department of Physiology, Feinberg School of Medicine, Northwestern University, 
      Chicago, IL 60611, USA. Electronic address: j-surmeier@northwestern.edu.
LA  - eng
GR  - R01 NS034696/NS/NINDS NIH HHS/United States
GR  - NS067414/NS/NINDS NIH HHS/United States
GR  - P50 MH074866/MH/NIMH NIH HHS/United States
GR  - NS034696/NS/NINDS NIH HHS/United States
GR  - R01 NS067414/NS/NINDS NIH HHS/United States
GR  - MH074866/MH/NIMH NIH HHS/United States
GR  - R37 NS034696/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuron
JT  - Neuron
JID - 8809320
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
CIN - Neuron. 2014 Jul 2;83(1):6-8. PMID: 24991950
MH  - Animals
MH  - Cerebral Cortex/pathology/*physiopathology
MH  - Corpus Striatum/pathology/*physiopathology
MH  - *Disease Models, Animal
MH  - Gene Knock-In Techniques
MH  - Huntington Disease/genetics/pathology/*physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Organ Culture Techniques
MH  - Receptor, trkB/antagonists & inhibitors/*deficiency/physiology
MH  - Signal Transduction/*genetics
PMC - PMC4131293
MID - NIHMS610266
EDAT- 2014/07/06 06:00
MHDA- 2014/09/03 06:00
PMCR- 2015/07/02
CRDT- 2014/07/04 06:00
PHST- 2014/05/21 00:00 [accepted]
PHST- 2014/07/04 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2014/09/03 06:00 [medline]
PHST- 2015/07/02 00:00 [pmc-release]
AID - S0896-6273(14)00447-4 [pii]
AID - 10.1016/j.neuron.2014.05.032 [doi]
PST - ppublish
SO  - Neuron. 2014 Jul 2;83(1):178-88. doi: 10.1016/j.neuron.2014.05.032.