EP3R-Expressing Glutamatergic Preoptic Neurons Mediate Inflammatory Fever.
| Autor: | Machado NLS; Department of Neurology, Division of Sleep Medicine, and Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, and., Bandaru SS; Department of Neurology, Division of Sleep Medicine, and Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, and., Abbott SBG; Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908., Saper CB; Department of Neurology, Division of Sleep Medicine, and Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, and csaper@bidmc.harvard.edu. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2020 Mar 18; Vol. 40 (12), pp. 2573-2588. Date of Electronic Publication: 2020 Feb 20. |
| DOI: | 10.1523/JNEUROSCI.2887-19.2020 |
| Abstrakt: | Fever is a common phenomenon during infection or inflammatory conditions. This stereotypic rise in body temperature (Tb) in response to inflammatory stimuli is a result of autonomic responses triggered by prostaglandin E2 action on EP3 receptors expressed by neurons in the median preoptic nucleus (MnPO EP3R neurons). To investigate the identity of MnPO EP3R neurons, we first used in situ hybridization to show coexpression of EP3R and the VGluT2 transporter in MnPO neurons. Retrograde tracing showed extensive direct projections from MnPO VGluT2 but few from MnPO Vgat neurons to a key site for fever production, the raphe pallidus. Ablation of MnPO VGluT2 but not MnPO Vgat neurons abolished fever responses but not changes in Tb induced by behavioral stress or thermal challenges. Finally, we crossed EP3R conditional knock-out mice with either VGluT2-IRES-cre or Vgat-IRES-cre mice and used both male and female mice to confirm that the neurons that express EP3R and mediate fever are glutamatergic, not GABAergic. This finding will require rethinking current concepts concerning the central thermoregulatory pathways based on the MnPO EP3R neurons being GABAergic. SIGNIFICANCE STATEMENT Body temperature is regulated by the CNS. The rise of the body temperature, or fever, is an important brain-orchestrated mechanism for fighting against infectious or inflammatory disease, and is tightly regulated by the neurons located in the median preoptic nucleus (MnPO). Here we demonstrate that excitatory MnPO neurons mediate fever and examine a potential central circuit underlying the development of fever responses. (Copyright © 2020 the authors.) |
| Databáze: | MEDLINE |
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