No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Recent studies in anesthetized rats suggest that autonomic effects relating to thermoregulation that are evoked from the preoptic area (POA) may be mediated through activation of neurons in the dorsomedial hypothalamus (DMH). Disinhibition of neurons in the DMH produces not only cardiovascular changes but also increases in plasma adrenocorticotropic hormone (ACTH) and locomotor activity mimicking those evoked by microinjection of muscimol, a GABAA receptor agonist and neuronal inhibitor, into the POA. Therefore, I tested the hypothesis that all of these effects evoked from the POA are mediated through neurons in the DMH by assessing the effect of bilateral microinjection of muscimol into the DMH on the changes evoked by microinjection of muscimol into the POA in conscious rats. In addition, I tested the hypothesis that neurons in the DMH mediate a specific response that is thought to signal through the POA, the activation of the HPA axis evoked by systemic administration of the inflammatory cytokine IL-1β. After injection of vehicle into the DMH, injection of muscimol into the POA elicited marked increases in heart rate, arterial pressure, body temperature, plasma ACTH and locomotor activity and also increased Fos expression in the hypothalamic paraventricular nucleus (PVN), a region known to control the release of ACTH from the adenohypophysis, and the raphe pallidus, a medullary region known to mediate POA-evoked sympathetic responses. Prior microinjection of muscimol into the DMH produced a modest depression of baseline heart rate, arterial pressure, and body temperature but completely abolished all changes evoked from the POA. Microinjection of muscimol just anterior to the DMH had no effect on POA-evoked autonomic and neuroendocrine changes. Inhibition of neuronal activity in the DMH only partially attenuated the increased activity of the HPA axis following systemic injections of IL-1β. Thus, neurons in the DMH mediate a diverse array of physiological and behavioral responses elicited from the POA, suggesting that the POA represents an important source of inhibitory tone to key neurons in the DMH. However, it is clear that the inflammatory cytokine IL-1β must employ other pathways that are DMH-, and possibly POA-, independent to activate the HPA axis.

published_or_final_version / abstract / Zoology / Master / Master of Philosophy

This study concerned the effects of short-term exposures to continuous (10 kv/meter) and pulsed 20 volts at 640 cps/100 msecs) electrostatic fields on the EEG recorded from external electrodes and hypothalamic activity recorded from implanted electrodes in rats. Each experiment lasted at least 90 minutes. The total energies of the waveforms recorded were integrated and printed out for plotting and analysis. Besides the brain activity, the ECG, respiration, and temperature of the animals were also monitored before, during,and after exposure to the electrostatic fields.

Exactly where in the hypothalamus is the adrenal-pituitary response to X-irradiation "triggered" or initiated? Moreover, does ionizing radiation act directly on specific centers in the brain or does it act indirectly via the production of some humoral agents? Finally, what role does the hypothalamus play in the radiation-syndrome? The purpose of the present study was to attempt to answer these questions by determining the effects of two stressor agents, X-irradiation and electrical stimulation applied either singly or together, on the activity of the adrenal-pituitary axis. The parameters measured were changes in plasma corticosterone, in circulating eosinopihils, and in adrenal gland weight.

The physiological mechanisms through which nutrition mediates its effects in controlling reproduction are not well characterized. Both neural and endocrine components have been implicated in the communication of nutritional status to the central nervous system. Leptin, a hormone synthesized and secreted mainly by adipocytes, is heavily involved in this communication network. The objectives of studies reported herein were 1) to determine the effects of short-term restriction of nutrients on circulating leptin, leptin gene expression in adipose tissue, and leptin receptor (LR) gene expression in the adenohypophysis of ovariectomized cows; and 2) to investigate the responsiveness of the hypothalamic-adenohypophyseal (AP) axis of fasted and non-fasted cattle to leptin. Studies demonstrated that circulating concentrations of leptin and leptin gene expression in subcutaneous adipose tissue are decreased by fasting. Although 2 to 3 days of fasting did not affect patterns of release of luteinizing hormone (LH), cerebroventricular infusions of leptin increased mean circulating concentrations of LH in fasted, but not normal-fed cows, without affecting frequency or amplitude of pulses of LH. In vitro studies were conducted to determine whether the in vivo effects of leptin could be accounted for at the hypothalamic and/or AP levels. Leptin did not affect the release of gonadotropin-releasing hormone (GnRH) from hypothalamic-infundibular explants from either normal-fed or fasted cattle. Moreover, leptin did not affect the basal release of LH from bovine AP cells or AP explants from normal-fed cows. However, leptin induced a higher basal release of LH from AP explants of fasted cows and increased GnRH-stimulated release of LH from AP explants of normal-fed cows. Results demonstrate that leptin acts directly at the AP level to modulate the secretion of LH, and its effects are dependent upon nutritional status. Cellular mechanisms associated with the increased responsiveness of gonadotropes to leptin in fasted cows were investigated. Expression of LR and suppressor of cytokine signaling-3 (SOCS-3) in the adenohypophysis did not account for the increased responsiveness of fasted cows to leptin. Therefore, although leptin clearly stimulates the hypothalamic-gonadotropic axis in nutrient-restricted cattle, it is unclear why cattle maintained under neutral or positive energy balance are resistant to leptin.

No description available.

No description available.

Canadians live in a society where the sun does not dictate the workday. Our lifestyles must shift to cater to the 24-hour demands of a fast paced global community. As a result our circadian rhythms are altered, leading to dysregulation of key physiological processes responsible for the maintenance of essential functions like energy homeostasis. Energy homeostasis is controlled by neuropeptide-expressing neurons within the hypothalamus. These neurons are affected by circulating hormone and nutrient levels in addition to their endogenous molecular clock machinery that controls cellular processes. Therefore, hypotheses were generated that non-SCN hypothalamic neurons express orexigenic neuropeptides in a rhythmic fashion without external influence from the SCN as a result of internal rhythmicity; and that elevated concentrations of palmitate, a ubiquitous saturated FFA common in a high fat diet, have direct influence on the mRNA levels of circadian clock components Bmal1, Clock, Per2, Rev-erbα and the potent orexigenic neuropeptides NPY, AgRP and ppGhrelin through mechanisms related to HAT, SIRT1 and AMPK. Using the mHypoE-44 neurons, a well characterized cell line that expresses the molecular clock and specific neuropeptides these hypotheses were explored in four studies. Neuropeptide expression within the mHypoE-44 neurons was determined to be rhythmic. NPY and NT demonstrate significant 24-hour rhythms. CRH and ppGhrelin mRNA cycled significantly in an ultradian fashion, oscillating approximately every 18 h. AgRP mRNA did not show a significant rhythm. We identified rhythmic binding of BMAL1 to the NPY promoter, suggesting clock-mediated control of neuropeptide expression. Bmal1 and Clock mRNA levels were elevated with palmitate, whereas Per2 and Rev-erbα mRNA showed significant decreases following palmitate treatment. Palmitate increased the acetylation of both BMAL1 and PER2 proteins. Alteration of AMPK activity altered the mRNA levels of all clock genes assayed and AMPK activation diminished the palmitate-induced changes in Bmal1 mRNA. Palmitate significantly elevated both NPY and ppGhrelin mRNA levels. Chemical modifiers that decrease acetylation altered these systems. AMPK activation reduced the palmitate-induced changes in NPY mRNA levels. These findings demonstrate that non-SCN neurons have rhythmic neuropeptide transcript levels. This thesis elucidates a direct effect of palmitate on the molecular clock and neuropeptide expression at the level of the hypothalamic neuron; and these findings highlight a role for HAT/SIRT1 activation and AMPK in these important processes, which ultimately contribute to the understanding of circadian dysregulation and energy balance.

Canadians live in a society where the sun does not dictate the workday. Our lifestyles must shift to cater to the 24-hour demands of a fast paced global community. As a result our circadian rhythms are altered, leading to dysregulation of key physiological processes responsible for the maintenance of essential functions like energy homeostasis. Energy homeostasis is controlled by neuropeptide-expressing neurons within the hypothalamus. These neurons are affected by circulating hormone and nutrient levels in addition to their endogenous molecular clock machinery that controls cellular processes. Therefore, hypotheses were generated that non-SCN hypothalamic neurons express orexigenic neuropeptides in a rhythmic fashion without external influence from the SCN as a result of internal rhythmicity; and that elevated concentrations of palmitate, a ubiquitous saturated FFA common in a high fat diet, have direct influence on the mRNA levels of circadian clock components Bmal1, Clock, Per2, Rev-erbα and the potent orexigenic neuropeptides NPY, AgRP and ppGhrelin through mechanisms related to HAT, SIRT1 and AMPK. Using the mHypoE-44 neurons, a well characterized cell line that expresses the molecular clock and specific neuropeptides these hypotheses were explored in four studies. Neuropeptide expression within the mHypoE-44 neurons was determined to be rhythmic. NPY and NT demonstrate significant 24-hour rhythms. CRH and ppGhrelin mRNA cycled significantly in an ultradian fashion, oscillating approximately every 18 h. AgRP mRNA did not show a significant rhythm. We identified rhythmic binding of BMAL1 to the NPY promoter, suggesting clock-mediated control of neuropeptide expression. Bmal1 and Clock mRNA levels were elevated with palmitate, whereas Per2 and Rev-erbα mRNA showed significant decreases following palmitate treatment. Palmitate increased the acetylation of both BMAL1 and PER2 proteins. Alteration of AMPK activity altered the mRNA levels of all clock genes assayed and AMPK activation diminished the palmitate-induced changes in Bmal1 mRNA. Palmitate significantly elevated both NPY and ppGhrelin mRNA levels. Chemical modifiers that decrease acetylation altered these systems. AMPK activation reduced the palmitate-induced changes in NPY mRNA levels. These findings demonstrate that non-SCN neurons have rhythmic neuropeptide transcript levels. This thesis elucidates a direct effect of palmitate on the molecular clock and neuropeptide expression at the level of the hypothalamic neuron; and these findings highlight a role for HAT/SIRT1 activation and AMPK in these important processes, which ultimately contribute to the understanding of circadian dysregulation and energy balance.