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@ARTICLE{Cui:893315,
author = {Cui, Di and Mesaros, Andrea and Burdeos, Gregor and Voigt,
Ingo and Giavalisco, Patrick and Hinze, Yvonne and Purrio,
Martin and Neumaier, Bernd and Drzezga, Alexander and Obata,
Yayoi and Endepols, Heike and Xu, Xiangru},
title = {{D}nmt3a2/{D}nmt3{L} {O}verexpression in the {D}opaminergic
{S}ystem of {M}ice {I}ncreases {E}xercise {B}ehavior through
{S}ignaling {C}hanges in the {H}ypothalamus},
journal = {International journal of molecular sciences},
volume = {21},
number = {17},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {FZJ-2021-02689},
pages = {6297 -},
year = {2020},
abstract = {Dnmt3a2, a de novo DNA methyltransferase, is induced by
neuronal activity and participates in long-term memory
formation with the increased expression of synaptic
plasticity genes. We wanted to determine if Dnmt3a2 with its
partner Dnmt3L may influence motor behavior via the
dopaminergic system. To this end, we generated a mouse line,
Dnmt3a2/3LDat/wt, with dopamine transporter (DAT) promotor
driven Dnmt3a2/3L overexpression. The mice were studied with
behavioral paradigms (e.g., cylinder test, open field, and
treadmill), brain slice patch clamp recordings, ex vivo
metabolite analysis, and in vivo positron emission
tomography (PET) using the dopaminergic tracer 6-[18F]FMT.
The results showed that spontaneous activity and exercise
performance were enhanced in Dnmt3a2/3LDat/wt mice compared
to Dnmt3a2/3Lwt/wt controls. Dopaminergic substantia nigra
pars compacta neurons of Dnmt3a2/3LDat/wt animals displayed
a higher fire frequency and excitability. However, dopamine
concentration was not increased in the striatum, and
dopamine metabolite concentration was even significantly
decreased. Striatal 6-[18F]FMT uptake, reflecting aromatic
L-amino acid decarboxylase activity, was the same in
Dnmt3a2/3LDat/wt mice and controls. [18F]FDG PET showed that
hypothalamic metabolic activity was tightly linked to motor
behavior in Dnmt3a2/3LDat/wt mice. Furthermore, dopamine
biosynthesis and motor-related metabolic activity were
correlated in the hypothalamus. Our findings suggest that
Dnmt3a2/3L, when overexpressed in dopaminergic neurons,
modulates motor performance via activation of the
nigrostriatal pathway. This does not involve increased
dopamine synthesis.},
cin = {INM-5 / INM-2},
ddc = {540},
cid = {I:(DE-Juel1)INM-5-20090406 / I:(DE-Juel1)INM-2-20090406},
pnm = {573 - Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)16},
pubmed = {32878077},
UT = {WOS:000569576000001},
doi = {10.3390/ijms21176297},
url = {https://juser.fz-juelich.de/record/893315},
}