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Reduced expression of the TrkB receptor in Huntington's disease mouse models and in human brain
Author(s) -
Ginés Silvia,
Bosch Miquel,
Marco Sonia,
Gavaldà Núria,
DíazHernández Miguel,
Lucas José J.,
Canals Josep M.,
Alberch Jordi
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04590.x
Subject(s) - tropomyosin receptor kinase b , huntingtin , neurotrophic factors , brain derived neurotrophic factor , neurotrophin , biology , neuroscience , mutant , receptor , microbiology and biotechnology , medicine , genetics , gene
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.