Abstract
Stress responses in mammals are mediated through specific hypothalamo-pituitary-adrenocortical (HPA) and sympathoadrenal (HSA) circuits activated by psychogenic and metabolic stressors. Since signaling through these circuits is itself a cellular stressor, the cellular stress response is a point of entry to identifying targets for pharmacological modulation of organismic stress perception and processing. The neuropeptide PACAP is an informational molecule that is released from stress-transducing neurons, and exerts post-synaptic effects required for completion of the stress response. Chromaffin cells and CNS neurons in culture, and PACAP-deficient mice in vivo, have been used to identify PACAP-responsive (in culture) and PACAP-dependent (in vivo) transcriptomic changes that occur in the adrenal gland, hypothalamus and pituitary upon activation of these circuits. Through this approach, we have learned that the stress response is PACAP-dependent at multiple HPA and HSA levels, and that novel factors that are potentially neuroprotective are induced by PACAP within the response circuit. These transcriptional responses are conveyed through non-canonical cyclic AMP- and/or calcium-initiated signaling pathways unique to the cellular stress response.
Published Version
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