In vivo characterization of pituitary adenylate cyclase-activating polypeptide in mouse olfactory epithelium

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Publication Type dissertation
School or College School of Medicine
Department Neurology
Author Stamm, Michelle L.
Title In vivo characterization of pituitary adenylate cyclase-activating polypeptide in mouse olfactory epithelium
Date 2011-12
Description The study of neurogenesis is important for understanding the causes of many developmental defects, and crucial for the prevention and treatment of neuronal degeneration and injury. The olfactory system is an excellent model for the study of neurogenesis due to its unique ability to continuously regenerate olfactory sensory neurons (OSNs), even in adults. Pituitary adenylate cyclaseactivating polypeptide (PACAP) functions in many aspects of neurogenesis and is present in the olfactory epithelium (OE). We examined the role of PACAP, in vivo, in the development and regeneration of the OE by comparing PACAP knock-out (KO) and wild-type (WT) mice. In early postnatal development, proliferation levels are reduced in PACAP KO mice but the number of OSNs is not different from WT mice. By 1 week of age, no differences between PACAP KO and WT mice were observed. Given that other growth factors may be present during development and could compensate for the absence of PACAP, we also examined adult OE. Although adult PACAP KO mice have normal food odorant detection, the OE exhibits decreased epithelial thickness due to loss of cells. However, immunostaining revealed no differences in OSN numbers between PACAP KO and WT mice, although expression levels for markers of OSNs were increased. Surprisingly, PACAP KO mice show increased proliferation compared to WT mice. Injury-induced degradation, resulting in iv regeneration of the OE, was also examined in adult PACAP KO and WT mice. Immediately after chemical insult, PACAP KO mice exhibited more inflammation than WT mice. A faster decline in OSNs, leading to quicker onset of anosmia, was seen in PACAP KO mice. In addition, PACAP KO mice recovered from anosmia more quickly, likely due to increased proliferation levels before insult. However, 1 week following insult there were no differences between PACAP KO and WT mice, and both groups were recovered functionally after 2 weeks. We conclude that PACAP has a minor influence promoting proliferation during OE development. PACAP is not required for adult proliferation, but is required for the survival and maintenance of adult OE. This study suggests PACAP may be important for future therapies aimed at promoting neuronal survival.
Type Text
Publisher University of Utah
Subject MESH Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Neurogenesis; Olfactory Mucosa; Mice, Knockout; Olfactory Bulb; Pituitary Adenylate Cyclase-Activating Polypeptide
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Relation is Version of Digital reproduction of In Vivo Characterization of Pituitary Adenylate Cyclase-Activating Polypeptide in Mouse Olfactory Epithelium. Spencer S. Eccles Health Sciences Library. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Michelle L Stamm 2011
Format Medium application/pdf
Format Extent 1,343,211 bytes
Source Original in Marriott Library Special Collections, QP6.5 2011.S83
ARK ark:/87278/s6sf64df
Setname ir_etd
Date Created 2014-06-09
Date Modified 2022-01-13
ID 196516
Reference URL
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