Campbell, Shona Elizabeth Candelaria (2025) Dissecting the role of prostaglandin E₂ EP2 receptor signaling in MCH neurons in sex-dependent modulation of anxiety, memory and hippocampal synaptic transmission under western diet. Masters thesis, Memorial University of Newfoundland.
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Abstract
Melanin-concentrating hormone (MCH) neurons are known to regulate energy balance, food intake, anxiety, memory, and cognition. Prostaglandin E₂ (PGE2) can depolarize these neurons via EP2 receptors under western diet (WD) conditions, which contributes to diet-induced obesity. To determine how WD-induced activation of MCH neurons affects other function of these cells, this research examined the sex- and diet-specific effects of EP2 receptor (EP2R) deletion in MCH neurons on anxiety-like behaviors, memory performance, and synaptic plasticity. Male and female mice with MCH neuron-specific EP2R knockout (KO) were assessed under chronic standard chow or WD conditions using behavioral assays and electrophysiological recordings. EP2R KO significantly reduced anxiety-like behaviors in male mice on a WD, evidenced by decreased thigmotaxis in the open field test, while differences in thigmotaxis were absent in all females and chow-fed males. In the novel object recognition test, male EP2R KO mice exhibited increased novel object preference under standard chow conditions compared to WD KO mice, while EP2R KO protected females from WD-induced memory impairments. Finally, electrophysiological experiments in transverse dorsal hippocampal brain slices revealed higher neurotransmitter release probability in female EP2R KO chow-fed mice, as well as an enhanced post-tetanic potentiation in chow-fed male EP2R KO mice compared to chow controls, while no changes were seen in long-term potentiation. These findings highlight the complex interplay between diet, sex, and EP2R signaling in MCH neurons. Thus, EP2Rs in MCH neurons may play a role in high-fat diet-induced changes in mood and cognitive function.
| Item Type: | Thesis (Masters) |
|---|---|
| URI: | http://research.library.mun.ca/id/eprint/16912 |
| Item ID: | 16912 |
| Additional Information: | Includes bibliographical references (pages 91-112) -- Restricted until February 26, 2026 |
| Keywords: | melanin-concentrating hormone, EP2 receptor, synaptic modulation, anxiety, memory |
| Department(s): | Medicine, Faculty of > Biomedical Sciences |
| Date: | May 2025 |
| Date Type: | Submission |
| Digital Object Identifier (DOI): | https://doi.org/10.48336/eqfx-w758 |
| Medical Subject Heading: | melanin-concentrating hormone; Diet, Western; Receptors, Prostaglandin; Anxiety; Memory |
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