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Translational profiling of mouse dopaminoceptive neurons reveals region-specific gene expression, exon usage, and striatal prostaglandin E2 modulatory effects.
Montalban, Enrica; Giralt, Albert; Taing, Lieng; Schut, Evelien H S; Supiot, Laura F; Castell, Laia; Nakamura, Yuki; de Pins, Benoit; Pelosi, Assunta; Goutebroze, Laurence; Tuduri, Pola; Wang, Wei; Neiburga, Katrina Daila; Vestito, Letizia; Castel, Julien; Luquet, Serge; Nairn, Angus C; Hervé, Denis; Heintz, Nathaniel; Martin, Claire; Greengard, Paul; Valjent, Emmanuel; Meye, Frank J; Gambardella, Nicolas; Roussarie, Jean-Pierre; Girault, Jean-Antoine.
Afiliação
  • Montalban E; Inserm UMR-S 1270, Paris, France.
  • Giralt A; Faculty of Sciences and Engineering, Sorbonne Université, Paris, France.
  • Taing L; Institut du Fer à Moulin, Paris, France.
  • Schut EHS; Université de Paris, CNRS, Unité de Biologie Fonctionnelle et Adaptative, Paris, France.
  • Supiot LF; Inserm UMR-S 1270, Paris, France.
  • Castell L; Faculty of Sciences and Engineering, Sorbonne Université, Paris, France.
  • Nakamura Y; Institut du Fer à Moulin, Paris, France.
  • de Pins B; Departament de Biomedicina, Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
  • Pelosi A; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain.
  • Goutebroze L; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
  • Tuduri P; Production and Validation Center of Advanced Therapies (Creatio), University of Barcelona, Barcelona, Spain.
  • Wang W; Inserm UMR-S 1270, Paris, France.
  • Neiburga KD; Faculty of Sciences and Engineering, Sorbonne Université, Paris, France.
  • Vestito L; Institut du Fer à Moulin, Paris, France.
  • Castel J; UMR1166, Faculté de Médecine, Sorbonne University, Paris, France.
  • Luquet S; Department of Translational Neuroscience, Brain Center, UMC Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Nairn AC; Department of Translational Neuroscience, Brain Center, UMC Utrecht, Utrecht University, Utrecht, The Netherlands.
  • Hervé D; IGF, CNRS, INSERM, University of Montpellier, Montpellier, France.
  • Heintz N; Department of Psychological and Brain Sciences, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
  • Martin C; Inserm UMR-S 1270, Paris, France.
  • Greengard P; Faculty of Sciences and Engineering, Sorbonne Université, Paris, France.
  • Valjent E; Institut du Fer à Moulin, Paris, France.
  • Meye FJ; Inserm UMR-S 1270, Paris, France.
  • Gambardella N; Faculty of Sciences and Engineering, Sorbonne Université, Paris, France.
  • Roussarie JP; Institut du Fer à Moulin, Paris, France.
  • Girault JA; Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot, Israel.
Mol Psychiatry ; 27(4): 2068-2079, 2022 04.
Article em En | MEDLINE | ID: mdl-35177825
ABSTRACT
Forebrain dopamine-sensitive (dopaminoceptive) neurons play a key role in movement, action selection, motivation, and working memory. Their activity is altered in Parkinson's disease, addiction, schizophrenia, and other conditions, and drugs that stimulate or antagonize dopamine receptors have major therapeutic applications. Yet, similarities and differences between the various neuronal populations sensitive to dopamine have not been systematically explored. To characterize them, we compared translating mRNAs in the dorsal striatum and nucleus accumbens neurons expressing D1 or D2 dopamine receptor and prefrontal cortex neurons expressing D1 receptor. We identified genome-wide cortico-striatal, striatal D1/D2 and dorso/ventral differences in the translating mRNA and isoform landscapes, which characterize dopaminoceptive neuronal populations. Expression patterns and network analyses identified novel transcription factors with presumptive roles in these differences. Prostaglandin E2 (PGE2) was a candidate upstream regulator in the dorsal striatum. We pharmacologically explored this hypothesis and showed that misoprostol, a PGE2 receptor agonist, decreased the excitability of D2 striatal projection neurons in slices, and diminished their activity in vivo during novel environment exploration. We found that misoprostol also modulates mouse behavior including by facilitating reversal learning. Our study provides powerful resources for characterizing dopamine target neurons, new information about striatal gene expression patterns and regulation. It also reveals the unforeseen role of PGE2 in the striatum as a potential neuromodulator and an attractive therapeutic target.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dinoprostona / Misoprostol Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dinoprostona / Misoprostol Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article