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The functional heterogeneity of PACAP: Stress, learning, and pathology
Journal article   Open access   Peer reviewed

The functional heterogeneity of PACAP: Stress, learning, and pathology

Abha K. Rajbhandari, Jessica R. Barson, Marieke R. Gilmartin, Sayamwong E. Hammack and Briana K. Chen
Neurobiology of learning and memory, v 203
25 Jun 2023
DOI: https://doi.org/10.1016/j.nlm.2023.107792
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.nlm.2023.107792View
Accepted (AM)Open Access (Publisher-Specific),  Open

Abstract

learning memory PAC1R PACAP Stress
•The neuropeptide PACAP regulates many biological and behavioral processes. •Targeting PACAP could innovate treatment for a variety of disorders. •Heterogeneity in PACAP signaling poses challenges for therapeutic development. •Nonetheless, harnessing the PACAP system may be a powerful strategy against disease. Pituitary adenylate cyclase-activating peptide (PACAP) is a highly conserved and widely expressed neuropeptide that has emerged as a key regulator of multiple neural and behavioral processes. PACAP systems, including the various PACAP receptor subtypes, have been implicated in neural circuits of learning and memory, stress, emotion, feeding, and pain. Dysregulation within these PACAP systems may play key roles in the etiology of pathological states associated with these circuits, and PACAP function has been implicated in stress-related psychopathology, feeding and metabolic disorders, and migraine. Accordingly, central PACAP systems may represent important therapeutic targets; however, substantial heterogeneity in PACAP systems related to the distribution of multiple PACAP isoforms across multiple brain regions, as well as multiple receptor subtypes with several isoforms, signaling pathways, and brain distributions, provides both challenges and opportunities for the development of new clinically-relevant strategies to target the PACAP system in health and disease. Here we review the heterogeneity of central PACAP systems, as well as the data implicating PACAP systems in clinically-relevant behavioral processes, with a particular focus on the considerable evidence implicating a role of PACAP in stress responding and learning and memory. We also review data suggesting that there are sex differences in PACAP function and its interactions with sex hormones. Finally, we discuss both the challenges and promise of harnessing the PACAP system in the development of new therapeutic avenues and highlight PACAP systems for their critical role in health and disease.

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16 citations in Web of Science
11 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Behavioral Sciences
Neurosciences
Psychology
Psychology, Multidisciplinary
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