title: C1 neurons mediate a stress-induced anti-inflammatory reflex in mice.
abstract: C1 neurons, located in the medulla oblongata, mediate adaptive autonomic responses to physical stressors (for example, hypotension, hemorrhage and presence of lipopolysaccharides). We describe here a powerful anti-inflammatory effect of restraint stress, mediated by C1 neurons: protection against renal ischemia-reperfusion injury. Restraint stress or optogenetic C1 neuron (C1) stimulation (10 min) protected mice from ischemia-reperfusion injury (IRI). The protection was reproduced by injecting splenic T cells that had been preincubated with noradrenaline or splenocytes harvested from stressed mice. Stress-induced IRI protection was absent in Chrna7 knockout (a7nAChR-/-) mice and greatly reduced by destroying or transiently inhibiting C1. The protection conferred by C1 stimulation was eliminated by splenectomy, ganglionic-blocker administration or β2-adrenergic receptor blockade. Although C1 stimulation elevated plasma corticosterone and increased both vagal and sympathetic nerve activity, C1-mediated IRI protection persisted after subdiaphragmatic vagotomy or corticosterone receptor blockade. Overall, acute stress attenuated IRI by activating a cholinergic, predominantly sympathetic, anti-inflammatory pathway. C1s were necessary and sufficient to mediate this effect.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Chikara
authors.initials: C
authors.lastname: Abe
authors.affiliation: Department of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Mabel A
authors.initials: MA
authors.lastname: Inglis
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Viar
authors.affiliation: Department of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Rosin
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Stornetta
authors.affiliation: Department of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Patrice G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D006339:Heart Rate / Q000502:physiology; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D012149:Restraint, Physical; D013156:Splenectomy; D013312:Stress, Physiological / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; C579166:Chrna7 protein, mouse; D011987:Receptors, Steroid; D064569:alpha7 Nicotinic Acetylcholine Receptor; C024357:corticosterone receptor; D003345:Corticosterone