PhD, University of Cincinnati, 2023, Medicine: Molecular, Cellular and Biochemical Pharmacology

Palatable food intake reduces physiological and emotional responses to stress – a phenomenon known as “comfort” feeding. However, the mechanisms by which palatable food blunts stress responses are not known and are important as overconsumption of palatable food contributes to the develop of obesity. To study these mechanisms, the Ulrich-Lai group previously developed a limited sucrose intake (LSI) feeding paradigm that reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to acute stress in male rats, and in female rats specifically during the proestrus/estrus (p/e) stage of the estrous cycle. This dissertation uses the LSI paradigm to test the hypotheses that HPA-dampening by LSI is impaired in the context of diet-induced obesity (chapters 2 and 3) and that cannabinoid receptor 1 (CB1R) signaling mediates HPA-dampening by LSI (chapter 4). We examined the HPA axis response to an acute restraint stressor in LSI-fed (vs. water control) rats that were maintained on either normal chow (thereby remaining lean) or a high-fat high-sugar Western diet (WD) (to produce diet-induced obesity, DIO) for 8 weeks prior to LSI (using 3% and 30% sucrose vs. water controls). Data from male and female rats are shown in chapters 3 and 4, respectively; the female data includes estrous cycle stage in the analysis. In both male and female rats, WD effectively increased body fat. Moreover, male chow-fed lean rats who received either 3% or 30% sucrose had a blunted plasma corticosterone response to restraint stress, but this effect was absent in male WD-fed rats, indicating that WD-obesity prevents HPA-dampening by LSI. In contrast, LSI did not alter post-stress plasma corticosterone in either chow (lean) or WD-fed (DIO) female rats, regardless of estrous cycle. Notably, the positive control condition (lean females given LSI using 30% sucrose and tested during p/e) did not show HPA axis dampening as seen in prior experiments. However, the female results are difficult to (open full item for complete abstract)

Committee: Yvonne Ulrich-Lai Ph.D. (Committee Chair); Steve Davidson Ph.D. (Committee Member); Eric Wohleb Ph.D. (Committee Member); Diego Perez-Tilve Ph.D. (Committee Member); Jayme McReynolds Ph.D. (Committee Member) Subjects: Medicine

PHD, Kent State University, 2018, College of Arts and Sciences / Department of Biological Sciences

Maternal behavior is an evolutionary innate behavior that supports the development and growth of the offspring. Caring for the young is not only critical for the survival of the species, the quality of maternal care directly influences the offspring's developing brain and social behaviors. In most mammals, maternal behavior is associated with dramatic changes in brain neurochemistry, physiology and behavior to ensure parental responsiveness. Rodent models are useful for studying the neural underpinnings of these behavioral shifts. The onset of maternal care in rodents occurs rapidly at the time of parturition and is mediated by numerous neurotransmitter systems. The synthesis of vasopressin (Avp), endocannabinoids (eCBs), and oxytocin (Oxt) rapidly increases at the time of parturition and all three neurotransmitter systems have been found to be important for regulating maternal behaviors. This dissertation set out to study the role of Avp, eCB and Oxt systems in the neural regulation of the onset of maternal behaviors.

Committee: Heather Caldwell (Advisor); Eric Mintz (Committee Member); John Johnson (Committee Member); MaryAnn Raghanti (Committee Member); Stephen Fountain (Committee Member) Subjects: Behavioral Sciences; Neurosciences

BS, Kent State University, 2013, College of Arts and Sciences / Department of Biological Sciences

While the acylethanolamide oleoylethanolamide (OEA) has been found in the human ovary, its effect on ovarian cells in particular has not been studied. This study investigated the effects of OEA and its metabolically stable analog AM3102 on the human ovarian cancer cell line OV2008. Cell culture experiments, western blotting, and fluorescence microscopy were performed, using OEA and various other reagents. Possible targets investigated include the phospholipase A2 signaling pathway, OEA cell receptors GPR119 and PPAR-alpha, and reactive oxygen species (ROS) levels. Results indicated that both OEA and AM3102 inhibit cell proliferation and induce apoptosis in OV2008 cells in serum-free medium. Novel evidence was also provided concerning OEA and its targets in the cell, including the possibility that PTK might have cellular targets, besides iPLA2 and cPLA2, which are unknown. Finally, results indicated OEA's involvement in the increase of membrane ROS could be a key factor in cell death, as toxicity was reversible through a-tocopherol (a lipid-soluble antioxidant) but not Trolox (its water-soluble analog). Continued investigation into the details of these signaling cascades is recommended to help to better our understanding of OEA as a possible inhibitor of proliferation in cancerous cells.

Committee: P Bagavandoss Dr. (Advisor); Robert Hamilton Dr. (Committee Member); Leslie Heaphy Dr. (Committee Member); Julie Cremeans-Smith Dr. (Committee Member) Subjects: Biology; Biomedical Research; Cellular Biology