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COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex

التفاصيل البيبلوغرافية
العنوان: COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex
المؤلفون: Elizabeth M. C. Hillman, Timothy H. Murphy, Xavier Toussay, Irmgard Tegeder, Eitan Anenberg, Anastassios Karagiannis, Bruno Cauli, Clotilde Lecrux, Patrick Chausson, Edith Hamel, Nerea Ferreirós, Fabrice Plaisier, Frédéric Jarlier, Sean A. Burgess, Alexandre Lacroix
المساهمون: Réseau cortical et couplage neurovasculaire = Cortical Network and Neurovascular (NPS-03), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Human Frontier Science Program [RGY0070/2007], Agence Nationale pour la Recherche [ANR 2011 MALZ 003 01], Deutsche Forschungsgemeinschaft [CRC1039 A3], Fondation pour la Recherche Medicale fellowship [FDT20100920106], IHU Institut de Neurosciences Translationelles de Paris [ANR-10-IAIHU-06], Fondation pour la Recherche sur le Cerveau/Rotary Club de France [AOE-7], Canadian Institutes of Health Research (CIHR) [MOP-84209, MOP-1267], Heart and Stroke Foundation of Canada, Heart and Stroke Foundation of British Columbia and Yukon, Heart and Stroke Foundation of Yukon, Djavad Mowafaghian Centre for Brain Health, France Alzheimer (ASTROinAD), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
المصدر: Journal of Neuroscience
Journal of Neuroscience, Society for Neuroscience, 2015, 35 (34), pp.11791-11810. ⟨10.1523/JNEUROSCI.0651-15.2015⟩
Lacroix, A, Toussay, X, Anenberg, E, Lecrux, C, Ferreirós, N, Karagiannis, A, Plaisier, F, Chausson, P, Jarlier, F, Burgess, S A, Hillman, E M C, Tegeder, I, Murphy, T H, Hamel, E & Cauli, B 2015, ' COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex ', Journal of Neuroscience, vol. 35, no. 34, pp. 11791-810 . https://doi.org/10.1523/JNEUROSCI.0651-15.2015
Journal of Neuroscience, 2015, 35 (34), pp.11791-11810. ⟨10.1523/JNEUROSCI.0651-15.2015⟩
بيانات النشر: HAL CCSD, 2015.
سنة النشر: 2015
مصطلحات موضوعية: Male, Cell type, Mice, 129 Strain, Prostaglandin E2 receptor, Prostaglandin, Mice, Transgenic, Stimulation, Biology, Dinoprostone, Rats, Sprague-Dawley, Mice, 03 medical and health sciences, chemistry.chemical_compound, Organ Culture Techniques, 0302 clinical medicine, pyramidal cells, medicine, Animals, Premovement neuronal activity, Rats, Wistar, Prostaglandin E2, Receptor, 030304 developmental biology, 0303 health sciences, interneurons, General Neuroscience, astrocytes, Articles, Rats, Mice, Inbred C57BL, Vasodilation, medicine.anatomical_structure, chemistry, Cyclooxygenase 2, Cerebral cortex, cyclooxygenase-2, cerebral cortex, Female, lipids (amino acids, peptides, and proteins), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery, medicine.drug
الوصف: UNLABELLED: Vasodilatory prostaglandins play a key role in neurovascular coupling (NVC), the tight link between neuronal activity and local cerebral blood flow, but their precise identity, cellular origin and the receptors involved remain unclear. Here we show in rats that NMDA-induced vasodilation and hemodynamic responses evoked by whisker stimulation involve cyclooxygenase-2 (COX-2) activity and activation of the prostaglandin E2 (PgE2) receptors EP2 and EP4. Using liquid chromatography-electrospray ionization-tandem mass spectrometry, we demonstrate that PgE2 is released by NMDA in cortical slices. The characterization of PgE2 producing cells by immunohistochemistry and single-cell reverse transcriptase-PCR revealed that pyramidal cells and not astrocytes are the main cell type equipped for PgE2 synthesis, one third expressing COX-2 systematically associated with a PgE2 synthase. Consistent with their central role in NVC, in vivo optogenetic stimulation of pyramidal cells evoked COX-2-dependent hyperemic responses in mice. These observations identify PgE2 as the main prostaglandin mediating sensory-evoked NVC, pyramidal cells as their principal source and vasodilatory EP2 and EP4 receptors as their targets.SIGNIFICANCE STATEMENT: Brain function critically depends on a permanent spatiotemporal match between neuronal activity and blood supply, known as NVC. In the cerebral cortex, prostaglandins are major contributors to NVC. However, their biochemical identity remains elusive and their cellular origins are still under debate. Although astrocytes can induce vasodilations through the release of prostaglandins, the recruitment of this pathway during sensory stimulation is questioned. Using multidisciplinary approaches from single-cell reverse transcriptase-PCR, mass spectrometry, to ex vivo and in vivo pharmacology and optogenetics, we provide compelling evidence identifying PgE2 as the main prostaglandin in NVC, pyramidal neurons as their main cellular source and the vasodilatory EP2 and EP4 receptors as their main targets. These original findings will certainly change the current view of NVC.
وصف الملف: application/pdf
اللغة: English
تدمد: 0270-6474
1529-2401
DOI: 10.1523/JNEUROSCI.0651-15.2015⟩
DOI: 10.1523/JNEUROSCI.0651-15.2015
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b98e970b723ebad9ef85e4e591ecea3a
https://hal.archives-ouvertes.fr/hal-01541357
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....b98e970b723ebad9ef85e4e591ecea3a
قاعدة البيانات: OpenAIRE
الوصف
تدمد:02706474
15292401
DOI:10.1523/JNEUROSCI.0651-15.2015⟩