Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules

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 fun...

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Bibliographic Details
Authors: 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
Format: article
Status:Published version
Publication Date:2014
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/117367
Online Access:https://hdl.handle.net/2445/117367
Access Level:Open access
Keyword:Dopamina
Neurotransmissors
Receptors de neurotransmissors
Olors
Expressió gènica
Regulació genètica
Dopamine
Neurotransmitters
Neurotransmitter receptors
Odors
Gene expression
Genetic regulation
Description
Summary: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.

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