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Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2021)

‘Homeostasis’ is the physiological process of maintaining a stable equilibrium, operating within optimal limits to promote health and prevent illness. Deviations from homeostasis can have adverse consequences for one’s health. However, physiological and behavioral needs vary markedly over the course of the day, necessitating that biological systems are adjusted correspondingly. Likewise, physiological needs change over the female reproductive cycle, with ovulation, pregnancy and fetal development, and parturition requiring specifically-timed patterns of hormone secretion regulated by the circadian system. Disruption to homeostasis, either by circadian misalignment or by exposure to stress, has marked, negative consequences for female reproductive health, including ovulation, pregnancy success and maintenance, and offspring development. The overarching goal of this dissertation research is to understand the neural and hormonal mechanisms underlying reproductive health and how these mechanisms are affected by disruption to homeostasis through circadian misalignment and stress. This dissertation considers two aspects of the female reproductive cycle, the ovulatory cycle and pregnancy. Despite a significant volume of knowledge detailing the circadian regulation of ovulation and the negative impact of stress of reproductive health, the mechanisms underlying these events remain poorly understood. Chapter 2 investigates the time-dependent sensitivity of the reproductive axis to the inhibitory neuropeptide RFamide-related peptide-3 (RFRP-3) in the control of the neuroendocrine events required for ovulation. Chapters 3-5 explore how stress hormones act on the brain, ovaries, and placenta to compromise pregnancy success and fetal development. These studies inform our understanding of the complex neural and endocrine networks regulating environmental and physiological processes involved in promoting female reproductive health.

    Cover page: Neural Circuits and Hormonal Mechanisms Underlying Female Reproduction
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2018)
    The circadian timing system orchestrates daily rhythms in physiology and behavior via the suprachiasmatic nucleus (SCN), the master brain clock. Because endocrine secretions have far-reaching influence on the brain and periphery, circadian regulation of hormones is essential for normal functioning and disruptions to circadian timing (e.g., irregular sleep patterns, limited exposure to sunlight, jet lag, nighttime light exposure) have detrimental health consequences. Herein, we provide an overview of circadian timing in three major endocrine axes, the hypothalamo-pituitary-gonadal (HPG), hypothalamo-pituitary-adrenal (HPA) and hypothalamo-pituitary-thyroid (HPT) axes, and then consider the negative health consequences of circadian disruptions in each of these systems. For example, disruptions to HPG axis circadian timing lead to a host of negative reproductive outcomes such as irregular menstrual cycles, low sperm density and increased rates of miscarriages and infertility. Dysregulation of HPA axis timing is associated with obesity and metabolic disease, whereas disruptions to the HPT axis are associated with dysregulated metabolic gene rhythms in the heart. Together, this overview underscores the significance of circadian endocrine rhythms in normal health and disease prevention.
      Cover page: Circadian control of neuroendocrine function: implications for health and disease
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2019)
      In spontaneously ovulating rodent species, the timing of the luteinising hormone (LH) surge is controlled by the master circadian pacemaker in the suprachiasmatic nucleus (SCN). The SCN initiates the LH surge via the coordinated control of two opposing neuropeptidergic systems that lie upstream of the gonadotrophin-releasing hormone (GnRH) neuronal system: the stimulatory peptide, kisspeptin, and the inhibitory peptide, RFamide-related peptide-3 (RFRP-3; the mammalian orthologue of avian gonadotrophin-inhibitory hormone [GnIH]). We have previously shown that the GnRH system exhibits time-dependent sensitivity to kisspeptin stimulation, further contributing to the precise timing of the LH surge. To examine whether this time-dependent sensitivity of the GnRH system is unique to kisspeptin or a more common mechanism of regulatory control, we explored daily changes in the response of the GnRH system to RFRP-3 inhibition. Female Syrian hamsters were ovariectomised to eliminate oestradiol (E2 )-negative-feedback and RFRP-3 or saline was centrally administered in the morning or late afternoon. LH concentrations and Lhβ mRNA expression did not differ between morning RFRP-3-and saline-treated groups, although they were markedly suppressed by RFRP-3 administration in the afternoon. However, RFRP-3 inhibition of circulating LH at the time of the surge does not appear to act via the GnRH system because no differences in medial preoptic area Gnrh or RFRP-3 receptor Gpr147 mRNA expression were observed. Rather, RFRP-3 suppressed arcuate nucleus Kiss1 mRNA expression and potentially impacted pituitary gonadotrophs directly. Taken together, these findings reveal time-dependent responsiveness of the reproductive axis to RFRP-3 inhibition, possibly via variation in the sensitivity of arcuate nucleus kisspeptin neurones to this neuropeptide.
        Cover page: Time‐of‐day‐dependent sensitivity of the reproductive axis to RFamide‐related peptide‐3 inhibition in female Syrian hamsters
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2020)
        Multiple neurocognitive systems contribute simultaneously to learning. For example, dopamine and basal ganglia (BG) systems are thought to support reinforcement learning (RL) by incrementally updating the value of choices, while the prefrontal cortex (PFC) contributes different computations, such as actively maintaining precise information in working memory (WM). It is commonly thought that WM and PFC show more protracted development than RL and BG systems, yet their contributions are rarely assessed in tandem. Here, we used a simple learning task to test how RL and WM contribute to changes in learning across adolescence. We tested 187 subjects ages 8 to 17 and 53 adults (25-30). Participants learned stimulus-action associations from feedback; the learning load was varied to be within or exceed WM capacity. Participants age 8-12 learned slower than participants age 13-17, and were more sensitive to load. We used computational modeling to estimate subjects' use of WM and RL processes. Surprisingly, we found more protracted changes in RL than WM during development. RL learning rate increased with age until age 18 and WM parameters showed more subtle, gender- and puberty-dependent changes early in adolescence. These results can inform education and intervention strategies based on the developmental science of learning.
          Cover page: Disentangling the systems contributing to changes in learning during adolescence
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2020)
          The authors regret that their article title was incorrectly spelled, and should have read as above. The authors would like to apologise for any inconvenience caused.
            Cover page: Corrigendum to “Disentangling the systems contributing to changes in learning during adolescence” [Dev. Cogn. Neurosci. 41, 2020, 100732]Creative Commons 'BY-NC-ND' version 4.0 license
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2022)
            Psychological stress, both leading up to and during pregnancy, is associated with increased risk for negative pregnancy outcomes. Although the neuroendocrine circuits that link the stress response to reduced sexual motivation and mating are well-described, the specific pathways by which stress negatively impacts gestational outcomes remain unclear. Using a mouse model of chronic psychological stress during pregnancy, we investigated 1) how chronic exposure to stress during gestation impacts maternal reproductive neuroendocrine circuitry, and 2) whether stress alters developmental outcomes for the fetus or placenta by mid-pregnancy. Focusing on the stress-responsive neuropeptide RFRP-3, we identified novel contacts between RFRP-3-immunoreactive (RFRP-3-ir) cells and tuberoinfundibular dopaminergic neurons in the arcuate nucleus, thus providing a potential pathway linking the neuroendocrine stress response directly to pituitary prolactin production and release. However, neither of these cell populations nor circulating levels of pituitary hormones were affected by chronic stress. Conversely, circulating levels of steroid hormones relevant to gestational outcomes (progesterone and corticosterone) were altered in chronically-stressed dams across gestation, and those dams were qualitatively more likely to experience delays in fetal development. Together, these findings suggest that, up until at least mid-pregnancy, mothers appear to be relatively resilient to the effects of elevated glucocorticoids on reproductive neuroendocrine system function. We conclude that understanding how chronic psychological stress impacts reproductive outcomes will require understanding individual susceptibility and identifying reliable neuroendocrine changes resulting from gestational stress.
              Cover page: Impact of Chronic Prenatal Stress on Maternal Neuroendocrine Function and Embryo and Placenta Development During Early-to-Mid-Pregnancy in MiceCreative Commons 'BY' version 4.0 license
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