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

Alice Grison, Silvia Zucchelli, Alice Urzì, Ilaria Zamparo, Dejan Lazarevic, Giovanni Pascarella, Paola Roncaglia, Alejandro Giorgetti, Paula Garcia-Esparcia, Christina Vlachouli, Roberto Simone, Francesca Persichetti, Alistair R R Forrest, Yoshihide Hayashizaki, Paolo Carloni, Isidro Ferrer, Claudia Lodovichi, Charles Plessy, Piero Carninci, Stefano Gustincich

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Article number729
JournalBMC Genomics
Volume15
Issue number1
DOIs
Publication statusPublished - Aug 27 2014

Fingerprint

Odorant Receptors
Dopaminergic Neurons
antineoplaston A10
Substantia Nigra
Parkinson Disease
Laser Capture Microdissection
Gene Expression
Neurons
Olfactory Mucosa
Nerve Degeneration
Ventral Tegmental Area
Brain
Mesencephalon
In Situ Hybridization
Schizophrenia
Odorants
Pharmacology
Ligands
Technology
Polymerase Chain Reaction

Keywords

  • Dopaminergic neurons
  • NanoCAGE
  • Odorant receptors
  • Odors
  • Ventral midbrain

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules. / 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 R R; Hayashizaki, Yoshihide; Carloni, Paolo; Ferrer, Isidro; Lodovichi, Claudia; Plessy, Charles; Carninci, Piero; Gustincich, Stefano.

In: BMC Genomics, Vol. 15, No. 1, 729, 27.08.2014.

Research output: Contribution to journalArticle

Grison, A, Zucchelli, S, Urzì, A, Zamparo, I, Lazarevic, D, Pascarella, G, Roncaglia, P, Giorgetti, A, Garcia-Esparcia, P, Vlachouli, C, Simone, R, Persichetti, F, Forrest, ARR, Hayashizaki, Y, Carloni, P, Ferrer, I, Lodovichi, C, Plessy, C, Carninci, P & Gustincich, S 2014, 'Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules', BMC Genomics, vol. 15, no. 1, 729. https://doi.org/10.1186/1471-2164-15-729
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 R R ; Hayashizaki, Yoshihide ; Carloni, Paolo ; Ferrer, Isidro ; Lodovichi, Claudia ; Plessy, Charles ; Carninci, Piero ; Gustincich, Stefano. / Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules. In: BMC Genomics. 2014 ; Vol. 15, No. 1.
@article{6b980acb00a24962bfad11f213de3b3f,
title = "Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules",
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.",
keywords = "Dopaminergic neurons, NanoCAGE, Odorant receptors, Odors, Ventral midbrain",
author = "Alice Grison and Silvia Zucchelli and Alice Urz{\`i} and Ilaria Zamparo and Dejan Lazarevic and Giovanni Pascarella and Paola Roncaglia and Alejandro Giorgetti and Paula Garcia-Esparcia and Christina Vlachouli and Roberto Simone and Francesca Persichetti and Forrest, {Alistair R R} and Yoshihide Hayashizaki and Paolo Carloni and Isidro Ferrer and Claudia Lodovichi and Charles Plessy and Piero Carninci and Stefano Gustincich",
year = "2014",
month = "8",
day = "27",
doi = "10.1186/1471-2164-15-729",
language = "English",
volume = "15",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules

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 R R

AU - Hayashizaki, Yoshihide

AU - Carloni, Paolo

AU - Ferrer, Isidro

AU - Lodovichi, Claudia

AU - Plessy, Charles

AU - Carninci, Piero

AU - Gustincich, Stefano

PY - 2014/8/27

Y1 - 2014/8/27

N2 - 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.

AB - 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.

KW - Dopaminergic neurons

KW - NanoCAGE

KW - Odorant receptors

KW - Odors

KW - Ventral midbrain

UR - http://www.scopus.com/inward/record.url?scp=84949115854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949115854&partnerID=8YFLogxK

U2 - 10.1186/1471-2164-15-729

DO - 10.1186/1471-2164-15-729

M3 - Article

AN - SCOPUS:84949115854

VL - 15

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 729

ER -