NIH Research Festival
–
PACAPergic neurotransmission in central and peripheral regulation of systemic and psychogenic stress responding
– Poster Session V
2:00 – 3:30 p.m.
FAES Terrace
NIMH
NEURO-19
Authors
- SZ Jiang
- T Mustafa
- LE Eiden
Abstract
PACAP is the major neurotransmitter released at the adrenomedullary synapse in response to systemic and psychogenic stressors, causing catecholamine (CA) release via activation of PAC1 receptors and simultaneously, regulation of the expression and activity of catecholamine biosynthetic enzymes (stimulus-secretion-synthesis coupling) (Stroth and Eiden, 2010; Stroth et al., 2013). In the brain, PACAPergic neurotransmission appears to be required for sustained activation of the hypothalamo-pituitary-adrenocortical (HPA) axis in response to psychogenic stressors, but not in response to systemic stressors, such as inflammation. It is not yet clear if PACAPergic signaling to activate the HPA axis is similar to that characterized peripherally. Chronic psychogenic stress, in the mouse, results in non-habituating corticosterone (CORT) elevation and development of depressive and anxious behaviors which are abrogated, or greatly attenuated, by PACAP, or PAC1, deficiency (Lehmann et al., 2013; Mustafa et al., in press). The site(s) of action of PACAP in brain may include synapses in hippocampus (contextual fear conditioning), extended amygdala (anxiety) and hypothalamus (regulation of CRH gene expression). Learning the sites of action of PACAP at PAC1 receptors in the brain, and how these are affected by elevation of catecholamines and CORT in the adrenal, will require additional genetic manipulations in the context of the functioning of identified and novel stressor-responsive circuits. Focusing PAC1 receptor pharmacology on treatment of affective disorders involving psychogenic stress, using rodent genetic models, will require a better understanding of the underlying cell signaling initiated by PACAP receptor occupancy, and its cell specificity in central and peripheral PACAP-receptive neurons.
Scientific Focus Area: Neuroscience
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