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Dissertation
The role of the paraventricular nucleus of the thalamus and pituitary adenylate cyclase activating polypeptide in binge-type eating
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2022
DOI:
https://doi.org/10.17918/00001097
Abstract
Binge eating disorder is the most common eating disorder in the United States, with more women affected than men. Both clinically and pre-clinically, it is characterized by the consumption of large amounts of food in a discrete time period. Currently, there are few effective pharmacological treatments for this disorder, so identification of novel pharmacotherapeutic targets is an urgent need. The neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), is densely expressed as its less-ubiquitous peptide isoform, PACAP-27, in the limbic paraventricular nucleus of the thalamus (PVT). While both PACAP and the PVT have independently been implicated in feeding behavior, they have not collectively been examined for their role in binge-type eating. This thesis examines the involvement of PVT PACAP in binge-type eating behavior. In both mice and rats, baseline gene expression of PVT PACAP was greater in females than in males. In rats, females were also found to have a significantly greater percentage of both PACAP-27+ and PACAP-38+ cells in the PVT than males. When mice were given limited access to Milk Chocolate Ensure Plus®, they developed binge-type eating - consuming significantly more calories during a 2-hour period of access than mice with access to chow only, and escalating their intake across sessions. Females engaged in this binge-type eating to a greater extent than males. Examining PVT PACAP gene expression in binge-type eating revealed that, in females, levels of PVT PACAP mRNA decreased immediately before a binge, while in males, they increased following a history of binge-type eating. Chemogenetic enhancement of PVT PACAP+ cell activity in binge eating mice inhibited binge-type eating, without influencing intake of simultaneously-available chow. These PVT PACAP+ cells innervated other limbic regions, including the nucleus accumbens shell and the bed nucleus of the stria terminalis. Together, the results of this thesis suggests that PACAP in the PVT may be an endogenous inhibitor of binge-type eating, likely acting through projections to other limbic brain regions. Thus, manipulation of the PVT PACAP system, particularly PACAP-27, which is not densely expressed outside of the PVT, should be investigated for its ability to ameliorate binge-type eating.
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Details
- Title
- The role of the paraventricular nucleus of the thalamus and pituitary adenylate cyclase activating polypeptide in binge-type eating
- Creators
- Genevieve Rose Curtis
- Contributors
- Jessica R. Barson (Advisor)Ramesh Raghupathi (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vii, 114 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991018528711004721