% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Siebzehnrbl:852456,
author = {Siebzehnrübl, Florian A. and Raber, Kerstin A. and Urbach,
Yvonne K. and Schulze-Krebs, Anja and Canneva, Fabio and
Moceri, Sandra and Habermeyer, Johanna and Achoui, Dalila
and Gupta, Bhavana and Steindler, Dennis A. and Stephan,
Michael and Nguyen, Huu Phuc and Bonin, Michael and Riess,
Olaf and Bauer, Andreas and Aigner, Ludwig and
Couillard-Despres, Sebastien and Paucar, Martin Arce and
Svenningsson, Per and Osmand, Alexander and Andreew,
Alexander and Zabel, Claus and Weiss, Andreas and Kuhn,
Rainer and Moussaoui, Saliha and Blockx, Ines and Van der
Linden, Annemie and Cheong, Rachel Y. and Roybon, Laurent
and Petersén, Åsa and von Hörsten, Stephan},
title = {{E}arly postnatal behavioral, cellular, and molecular
changes in models of {H}untington disease are reversible by
{HDAC} inhibition},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {115},
number = {37},
issn = {1091-6490},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {FZJ-2018-05402},
pages = {E8765 - E8774},
year = {2018},
abstract = {Huntington disease (HD) is an autosomal dominant
neurodegenerative disorder caused by expanded CAG repeats in
the huntingtin gene (HTT). Although mutant HTT is expressed
during embryonic development and throughout life, clinical
HD usually manifests later in adulthood. A number of studies
document neurodevelopmental changes associated with mutant
HTT, but whether these are reversible under therapy remains
unclear. Here, we identify very early behavioral, molecular,
and cellular changes in preweaning transgenic HD rats and
mice. Reduced ultrasonic vocalization, loss of prepulse
inhibition, and increased risk taking are accompanied by
disturbances of dopaminergic regulation in vivo, reduced
neuronal differentiation capacity in subventricular zone
stem/progenitor cells, and impaired neuronal and
oligodendrocyte differentiation of mouse embryo-derived
neural stem cells in vitro. Interventional treatment of this
early phenotype with the histone deacetylase inhibitor
(HDACi) LBH589 led to significant improvement in behavioral
changes and markers of dopaminergic neurotransmission and
complete reversal of aberrant neuronal differentiation in
vitro and in vivo. Our data support the notion that
neurodevelopmental changes contribute to the prodromal phase
of HD and that early, presymptomatic intervention using
HDACi may represent a promising novel treatment approach for
HD.},
cin = {INM-2},
ddc = {000},
cid = {I:(DE-Juel1)INM-2-20090406},
pnm = {573 - Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30150378},
UT = {WOS:000444257200022},
doi = {10.1073/pnas.1807962115},
url = {https://juser.fz-juelich.de/record/852456},
}