PMID- 16487146
OWN - NLM
STAT- MEDLINE
DCOM- 20060509
LR  - 20161124
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 23
IP  - 3
DP  - 2006 Feb
TI  - Reduced expression of the TrkB receptor in Huntington's disease mouse models and 
      in human brain.
PG  - 649-58
AB  - Deficits of neurotrophic support caused by reduced levels of brain-derived 
      neurotrophic factor (BDNF) have been implicated in the selective vulnerability of 
      striatal neurones in Huntington's disease (HD). Therapeutic strategies based on 
      BDNF administration have been proposed to slow or prevent the disease 
      progression. However, the effectiveness of BDNF may depend on the proper 
      expression of its receptor TrkB. In this study, we analysed the expression of 
      TrkB in several HD models and in postmortem HD brains. We found a specific 
      reduction of TrkB receptors in transgenic exon-1 and full-length knock-in HD 
      mouse models and also in the motor cortex and caudate nucleus of HD brains. Our 
      findings also demonstrated that continuous expression of mutant huntingtin is 
      required to down-regulate TrkB levels. This was shown by findings in an inducible 
      HD mouse model showing rescue of TrkB by turning off mutant huntingtin 
      expression. Interestingly, the length of the polyglutamine tract in huntingtin 
      appears to modulate the reduction of TrkB. Finally, to analyse the effect of BDNF 
      in TrkB we compared TrkB expression in mutant huntingtin R6/1 and double mutant 
      (R6/1 : BDNF+/-) mice. Similar TrkB expression was found in both transgenic mice 
      suggesting that reduced TrkB is not a direct consequence of decreased BDNF. 
      Therefore, taken together our findings identify TrkB as an additional component 
      that potentially might contribute to the altered neurotrophic support in HD.
FAU - Gines, Silvia
AU  - Gines S
AD  - Departament de Biologia Cel.lular i Anatomia Patologica, Facultat de Medicina, 
      Universitat de Barcelona, Casanova 143, E-08036 Barcelona, Spain.
FAU - Bosch, Miquel
AU  - Bosch M
FAU - Marco, Sonia
AU  - Marco S
FAU - Gavalda, Nuria
AU  - Gavalda N
FAU - Diaz-Hernandez, Miguel
AU  - Diaz-Hernandez M
FAU - Lucas, Jose J
AU  - Lucas JJ
FAU - Canals, Josep M
AU  - Canals JM
FAU - Alberch, Jordi
AU  - Alberch J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (HTT protein, human)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Mutant Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Blotting, Western/methods
MH  - Brain/*metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism/pharmacology
MH  - Cell Count/methods
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Exons/genetics
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Humans
MH  - Huntingtin Protein
MH  - Huntington Disease/genetics/*metabolism/pathology
MH  - In Situ Hybridization/methods
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutant Proteins/metabolism
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/drug effects/metabolism
MH  - Nuclear Proteins/metabolism
MH  - Postmortem Changes
MH  - RNA, Messenger/metabolism
MH  - Receptor, trkB/genetics/*metabolism
EDAT- 2006/02/21 09:00
MHDA- 2006/05/10 09:00
CRDT- 2006/02/21 09:00
PHST- 2006/02/21 09:00 [pubmed]
PHST- 2006/05/10 09:00 [medline]
PHST- 2006/02/21 09:00 [entrez]
AID - EJN4590 [pii]
AID - 10.1111/j.1460-9568.2006.04590.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2006 Feb;23(3):649-58. doi: 10.1111/j.1460-9568.2006.04590.x.