PhD, University of Cincinnati, 2017, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary

Many individuals increase their intake of tasty, high-calorie foods during times of stress. In turn, these palatable foods can reduce physiological and psychological measures of stress, a concept reflected in the term `comfort food.' Obesity is one of the major public health issues facing the United States, and stress eating may be a contributing factor. Thus, investigating the mechanisms behind palatable food-mediated stress relief could provide important insights into treatments or prevention of obesity-related disorders. A limited sucrose intake (LSI) paradigm of palatable foods has been shown to reduce stress responses in male rats through a basolateral amygdala (BLA) mediated neurocircuit. However, women may be more prone to `comfort feeding' than men, and these eating behaviors may fluctuate across the menstrual cycle. This suggests there may be sex differences in how palatable food affects stress responses. It is unknown if palatable foods reduce stress responses in female rats, and if the effects vary with estrous cycle. Therefore, we characterized the effects of limited sucrose intake on stress responses in female rats. We found that a history of LSI reduces HPA axis responsivity and behavioral anxiety; notably this stress blunting is estrous-cycle dependent. LSI only reduces stress responses during the proestrus/estrus (P/E) stage of the estrous cycle, and not the diestrus 1/diestrus 2 (D1/D2) stage. This suggests fluctuating levels of gonadal hormones may be interacting with palatable foods to modulate stress responses. We used traditional neuroanatomical methods and innovative mathematical modeling techniques to identify a potential neurocircuit underlying this cycle-specific stress relief. We found estrous cycle-specific effects of LSI in the BLA, central amygdala, and the bed nucleus of the stria terminalis. Furthermore, Bayesian modeling, which was used to analyze predicted relationships among multiple brain regions, indicated that during P/E LSI (open full item for complete abstract)

Committee: Teresa Reyes Ph.D. (Committee Chair); James Herman Ph.D. (Committee Member); Brent Myers (Committee Member); Matia Solomon Ph.D. (Committee Member); Yvonne Ulrich-Lai Ph.D. (Committee Member) Subjects: Neurology

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, University of Cincinnati, 2010, Medicine : Neuroscience/Medical Science Scholars Interdisiplinary

Stress, a real or perceived threat to homeostasis, elicits responses from the HPA axis, triggers the sympathetic branch of the autonomic system, and elicits anxiety-related behaviors. These responses are heavily modulated by forebrain inputs, including the basolateral amygdala (BLA). Palatable food consumption, specifically sucrose snacking, results in collective stress relief, dampening the HPA axis, autonomic, and mood/behavioral responses to stress. In fact, consumption of palatable food is widely used as a kind of “self medication” for stress relief, which may lead to over-consumption and subsequently may contribute to the obesity epidemic. Understanding the mechanisms by which palatable food affects brain regions like the BLA to buffer the stress response may help develop stress interventions without the side-effect of obesity and other weight-related health problems. Using a rat model of palatable snacking, these studies tested the hypothesis that a history of palatable snacking causes persistent alterations in BLA signaling and snacking-induced reductions in the HPA response to stress. These data show that 1) palatable snacking induces numerous indices of synaptic remodeling (i.e. synaptophysin, deltaFosB) in stress and reward brain circuitry; 2) palatable snacking causes a lasting decrease in the hormonal response to stress that is accompanied by persistent alterations in BLA signaling; and 3) calcium calmodulin kinase II alpha (CaMKII) activity within the BLA is not necessary for palatable snacking-induced stress buffering but, in contrast, is responsible for limiting the stress-reducing properties of palatable snacking. The current studies contribute two major ideas to the fields of stress and obesity research. 1) Chronic intake of comfort food causes lasting changes in the brain. In particular, a discrete pathway of forebrain reward and stress regulatory brain regions undergoes synaptic changes after palatable snacking. This work implicates a potential me (open full item for complete abstract)

Committee: James Herman PhD (Committee Chair); Stephen Benoit PhD (Committee Member); David D'Alessio MD (Committee Member); Stephen Woods PhD (Committee Member); Yvonne Ulrich-Lai PhD (Committee Member) Subjects: Neurology