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Title: Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules
Author: Grison, Alice
Zucchelli, Silvia
Urzì, Alice
Zamparo, Ilaria
Lazarevic, Dejan
Pascarella, Giovanni
Roncaglia, Paola
Giorgetti, Alejandro
Garcia Esparcia, Paula
Vlachouli, Christina
Simone, Roberto
Persichetti, Francesca
Forrest, Alistair RR
Hayashizaki, Yoshihide
Carloni, Paolo
Ferrer, Isidro (Ferrer Abizanda)
Lodovichi, Claudia
Plessy, Charles
FANTOM Consortium
Carninci, Piero
Gustincich, Stefano
Keywords: Dopamina
Receptors de neurotransmissors
Expressió gènica
Regulació genètica
Neurotransmitter receptors
Gene expression
Genetic regulation
Issue Date: 1-Aug-2014
Publisher: BioMed Central
Abstract: Background: the 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. Results: by 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. Conclusions: our study indicates that mDA neurons express ORs and respond to odor-like molecules providing new opportunities for pharmacological intervention in disease.
Note: Reproducció del document publicat a:
It is part of: Bmc Genomics, 2014, vol. 15, p. 729
Related resource:
ISSN: 1471-2164
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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