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@ARTICLE{Grison:201333,
author = {Grison, Alice and Zucchelli, Silvia and Urzì, Alice and
Zamparo, Ilaria and Lazarevic, Dejan and Pascarella,
Giovanni and Roncaglia, Paola and Giorgetti, Alejandro and
Garcia-Esparcia, Paula and Vlachouli, Christina and Simone,
Roberto and Persichetti, Francesca and Forrest, Alistair RR
and Hayashizaki, Yoshihide and Carloni, Paolo and Ferrer,
Isidro and Lodovichi, Claudia and Plessy, Charles and
Carninci, Piero and Gustincich, Stefano},
title = {{M}esencephalic dopaminergic neurons express a repertoire
of olfactory receptors and respond to odorant-like
molecules},
journal = {BMC genomics},
volume = {15},
number = {1},
issn = {1471-2164},
address = {London},
publisher = {BioMed Central},
reportid = {FZJ-2015-03630},
pages = {729 -},
year = {2014},
abstract = {BackgroundThe mesencephalic dopaminergic (mDA) cell system
is composed of two major groups of projecting cells in the
Substantia Nigra (SN) (A9 neurons) and the Ventral Tegmental
Area (VTA) (A10 cells). Selective degeneration of A9 neurons
occurs in Parkinson’s disease (PD) while abnormal function
of A10 cells has been linked to schizophrenia, attention
deficit and addiction. The molecular basis that underlies
selective vulnerability of A9 and A10 neurons is presently
unknown.ResultsBy taking advantage of transgenic labeling,
laser capture microdissection coupled to nano Cap-Analysis
of Gene Expression (nanoCAGE) technology on isolated A9 and
A10 cells, we found that a subset of Olfactory Receptors
(OR)s is expressed in mDA neurons. Gene expression analysis
was integrated with the FANTOM5 Helicos CAGE sequencing
datasets, showing the presence of these ORs in selected
tissues and brain areas outside of the olfactory epithelium.
OR expression in the mesencephalon was validated by RT-PCR
and in situ hybridization. By screening 16 potential ligands
on 5 mDA ORs recombinantly expressed in an heterologous in
vitro system, we identified carvone enantiomers as agonists
at Olfr287 and able to evoke an intracellular Ca2+ increase
in solitary mDA neurons. ORs were found expressed in human
SN and down-regulated in PD post mortem
brains.ConclusionsOur study indicates that mDA neurons
express ORs and respond to odor-like molecules providing new
opportunities for pharmacological intervention in disease.},
cin = {INM-9 / IAS-5 / GRS},
ddc = {570},
cid = {I:(DE-Juel1)INM-9-20140121 / I:(DE-Juel1)IAS-5-20120330 /
I:(DE-Juel1)GRS-20100316},
pnm = {899 - ohne Topic (POF2-899)},
pid = {G:(DE-HGF)POF2-899},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000341327800001},
pubmed = {pmid:25164183},
doi = {10.1186/1471-2164-15-729},
url = {https://juser.fz-juelich.de/record/201333},
}