?Neural control of cytoprotective mechanisms?

RAYES DIEGO

Rosario

Congreso; IBRO Symposium Neural mechanism of aging, stress and neurodegeneration Second Latin American Worm Meeting.; 2020

IBR

An animal uses different survival strategies to cope withlife-threatening situations. For instance, it can engage in a rapid andenergy-demanding ?fight-or-flight? response when encountering a predator, or itcan induce the gradual and long-lasting activation of highly conservedcytoprotective processes in response to environmental stressors such ashypoxia, heat, oxidative stress, or food shortage.  In animals across the evolutionary spectrumthe continued activation of the fight-or-flight response weakens the animal?sresistance to environmental challenges. In humans, for instance, the recurrent experience of stress in patientsthat suffer from post-traumatic stress disorder (PTSD) has been associated withdecreased antioxidant capacity, accelerated aging and increased susceptibilityto metabolic, cardiovascular and infectious diseases.  However, the molecular and cellularmechanisms that regulate the trade-off between flight response and long-termstressors are poorly understood.  Here weshow that repeated induction of the C. elegans flight response shortenslifespan and inhibits conserved cytoprotective mechanisms.  The flight response activates neurons thatrelease tyramine, the invertebrate analog of adrenaline/noradrenaline.  Tyramine stimulates the DAF-2/Insulin/IGF-1pathway and precludes the induction of stress response genes by activating anadrenergic-like receptor in the intestine. In contrast, long-term environmental stressors, such as heat oroxidative stress, reduce tyramine release allowing the induction ofcytoprotective genes.  These findingsdemonstrate that a neural stress-hormone supplies a state-dependent neuralswitch between acute flight and long-term environmental stress responses andprovides mechanistic insights into how the flight response impairs cellulardefense systems and accelerates aging