TY  - JOUR
AU  - Grison, Alice
AU  - Zucchelli, Silvia
AU  - Urzì, Alice
AU  - Zamparo, Ilaria
AU  - Lazarevic, Dejan
AU  - Pascarella, Giovanni
AU  - Roncaglia, Paola
AU  - Giorgetti, Alejandro
AU  - Garcia-Esparcia, Paula
AU  - Vlachouli, Christina
AU  - Simone, Roberto
AU  - Persichetti, Francesca
AU  - Forrest, Alistair RR
AU  - Hayashizaki, Yoshihide
AU  - Carloni, Paolo
AU  - Ferrer, Isidro
AU  - Lodovichi, Claudia
AU  - Plessy, Charles
AU  - Carninci, Piero
AU  - Gustincich, Stefano
TI  - Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules
JO  - BMC genomics
VL  - 15
IS  - 1
SN  - 1471-2164
CY  - London
PB  - BioMed Central
M1  - FZJ-2015-03630
SP  - 729 -
PY  - 2014
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000341327800001
C6  - pmid:25164183
DO  - DOI:10.1186/1471-2164-15-729
UR  - https://juser.fz-juelich.de/record/201333
ER  -