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Nat Neurosci. 2017 May;20(5):700-707. doi: 10.1038/nn.4526. Epub 2017 Mar 13.

C1 neurons mediate a stress-induced anti-inflammatory reflex in mice.

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Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA.
Department of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia, USA.


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.

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