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bioRxiv · 10.1101/294645

Acute-stress impairs cytoprotective mechanisms through neural inhibition of the insulin pathway

De Rosa, M. J.·Veuthey, T.·Florman, J.·Grant, J.·Blanco, G.·Andersen, N.·Donnelly, J.·Rayes, D.·Alkema, M.
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Abstract

Persistent activation of the \"fight-or-flight\" response accelerates aging and increases the susceptibility to disease. We show that repeated induction of the C. elegans flight response inhibits conserved cytoprotective mechanisms. This acute-stress response activates neurons that release tyramine, the invertebrate analog of adrenaline/noradrenaline. Tyramine stimulates the DAF-2/Insulin/IGF-1 pathway and precludes the nuclear translocation of the DAF-16/FOXO transcription factor through the activation of an adrenergic-like receptor TYRA-3 in the intestine. In contrast, environmental long-term stressors, such as heat or oxidative stress, reduce tyramine release allowing the induction of FOXO-dependent cytoprotective genes. These findings demonstrate how a neural stress-hormone signaling provides a state-dependent neural switch between acute and long-term stress responses, and provide mechanistic insights how acute stress impairs cellular defensive systems.\n\nOne Sentence Summary: The \"fight-or-flight\" response reduces resistance to environmental challenges.

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De Rosa, M. J., Veuthey, T., Florman, J., Grant, J., Blanco, G., Andersen, N., Donnelly, J., Rayes, D., Alkema, M.. 2018-04-24. Acute-stress impairs cytoprotective mechanisms through neural inhibition of the insulin pathway. https://doi.org/10.1101/294645

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