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PACAP Expression and Plasticity in the Peripheral Nervous System

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Pituitary Adenylate Cyclase Activating Polypeptide — PACAP

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 11))

Abstract

Pituitary adenylate cyclase activating polypeptide (Adcyap1; PACAP) is a well-studied neural and endocrine pleiotropic peptide important in development and the homeostatic regulation of many physiological systems. Accordingly, PACAP and its cognate PAC1 receptor (Adcyap1r1) are localized in many central nervous system (CNS) regions and widely distributed in the peripheral nervous system (PNS). PACAP has been identified in a population of small nociceptive neurons in the dorsal root ganglion (DRG) targeting many peripheral tissues. PACAP-immunoreactive preganglionic sympathetic and parasympathetic nerve fibers densely innervate a variety of autonomic and enteric ganglia. Furthermore, a small fraction of the autonomic and enteric postganglionic neurons also endogenously express PACAP. Notably, PACAP belongs to a cohort of neuroplasticity peptides, and PNS insult invariably induces PACAP expression in the affected neurons. Axotomy, nerve crush, inflammation, and neural tissue explant paradigms can dramatically induce neuronal PACAP transcripts, immunoreactivity, content, and cell numbers. This plasticity in PACAP expression has been best appreciated in studies using the PACAP-EGFP transgenic mouse line. The mechanisms driving PACAP expression after insults are not well understood, but likely reflect the aggregate effects of cytokine/inflammatory activation signals at the injury site and an abrogation of retrograde signaling from the target tissues. The few comparative studies suggest that the mechanistic signatures for peptide induction may differ among the various neural systems. This induction of PACAP expression in physiological insults has been implicated to participate in fiber regeneration and anti-inflammatory responses, but PACAP neuroplasticity may also have broader roles in maintaining neurocircuit homeostasis.

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Acknowledgments

We thank Galen Missig, Beatrice M. Girard, Anton Kurtz, and Kristin C. Schutz for technical support in some of the studies. This work was supported by grants NS-01636 (KMB), HD-27468 and MH-096764 (VM), DK-051369, DK-060481 and DK-065989 (MAV), NS-23978 and HL-65481 (RLP), and funds from the University of Vermont (UVM) Center of Biomedical Research Excellence (Neuroscience COBRE, NCRR P30 RR032135/NIGMS P30 GM103498).

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Authors and Affiliations

  1. Department of Neurological Sciences, University of Vermont College of Medicine, 149 Beaumont Avenue, Burlington, VT, 05405, USA

    Karen M. Braas, Rodney L. Parsons, Margaret A. Vizzard & Victor May

  2. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, 635 South Charles E. Young Drive NRB 345, Los Angeles, CA, 90095, USA

    James A. Waschek

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  1. Karen M. Braas
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Correspondence to Victor May .

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Editors and Affiliations

  1. Department of Anatomy MTA-PTE “Lendulet” PACAP Research Team, University of Pecs, Pecs, Hungary

    Dora Reglodi

  2. Department of Anatomy MTA-PTE “Lendulet” PACAP Research Team, University of Pecs, Pecs, Hungary

    Andrea Tamas

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Braas, K.M., Parsons, R.L., Vizzard, M.A., Waschek, J.A., May, V. (2016). PACAP Expression and Plasticity in the Peripheral Nervous System. In: Reglodi, D., Tamas, A. (eds) Pituitary Adenylate Cyclase Activating Polypeptide — PACAP. Current Topics in Neurotoxicity, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-319-35135-3_33

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