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CENTRAL AND PERIPHERAL REGULATION OF CIRCADIAN GASTROINTESTINAL RHYTHMSMalloy, Jaclyn 01 January 2012 (has links)
Circadian clocks are responsible for daily rhythms in gastrointestinal function which are vital for normal digestive rhythms and health. The present study examines the roles of the circadian pacemaker, the suprachiasmatic nuclei (SCN), and the sympathetic nervous system in regulation of circadian gastrointestinal rhythms in Mus musculus. Surgical ablation of the SCN abolishes circadian locomotor, feeding, and stool output rhythms when animals are presented with food ad libitum, while restricted feeding reestablishes these rhythms temporarily. In intact mice, chemical sympathectomy with 6- hydroxydopamine has no effect on feeding and locomotor rhythmicity, but attenuates stool output rhythms. Again, restricted feeding reestablishes these rhythms. Ex vivo, intestinal tissue from mPer2LUC knockin mice expresses circadian rhythms of luciferase bioluminescence. 6-hydroxydopamine has little effect upon these rhythms, but timed administration of β−adrenergic agonist isoproterenol causes a phase-dependent phase shift in PERIOD2 expression rhythms. Collectively, the data suggest the SCN are required to maintain feeding, locomotor and stool output rhythms during ad libitum conditions, acting at least in part through daily activation of sympathetic activity. Even so, this input is not necessary for entrainment to timed feeding, which may be the province of oscillators within the intestines themselves or other components of the gastrointestinal system.
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Ex Vivo Evaluation of Myocardial Beta-Adrenergic Receptors in High-Fat Fed STZ and ZDF Models of Diabetes Using [3H]-CGP12177Haley, James M. 20 December 2013 (has links)
Diabetes mellitus (DM) and hyperglycemia contribute to sympathetic nervous system (SNS) activation and cardiovascular dysfunction. SNS activation and increased norepinephrine levels downregulate cardiac β-adrenergic receptors (β-AR). The ADMIRE-HF trial identified reduced cardiac SNS innervation as an independent prognostic marker in heart failure. The β-AR antagonist [3H]-CGP12177 was used to quantify cardiac β-AR in ex vivo biodistribution studies in streptozotocin (STZ)-treated rats after 8 weeks of sustained hyperglycemia, and in the Zucker Diabetic Fatty (ZDF) rat model of type-2 diabetes at the onset of hyperglycemia (10 weeks of age) and after a sustained period of hyperglycemia (16 weeks of age). In some STZ rats, insulin was provided at the onset of hyperglycemia, or after a sustained period of hyperglycemia. Insulin treatment at both time points prevented reduced [3H]-CGP12177 binding (33-38% compared to controls) observed in STZ hyperglycemics. ZDF β-ARs were intact at 10 weeks but became reduced (16-25% relative to the Zucker leans) following 6 weeks of hyperglycemia. This work supports that cardiac β-AR are reduced in models of DM and that restoring insulin signalling to maintain glycemic control can normalize β-AR density whether provided early or after a period of sustained hyperglycemia.
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PLASTICITY OF ADRENAL CHROMAFFIN CELL FUNCTION DURING INFLAMMATION AND EXPOSURE TO MICROBE-ASSOCIATED MOLECULAR PATTERNSLukewich, Mark 20 August 2013 (has links)
The sympathetic nervous system (SNS) is part of an integrative network that functions to restore homeostasis following injury and infection. The SNS provides negative feedback control over inflammation through the secretion of catecholamines from postganglionic sympathetic neurons and adrenal chromaffin cells (ACCs). Central autonomic structures receive information regarding the inflammatory status of the body and reflexively modulate SNS activity. Evidence suggests that inflammation and infection can also directly regulate ACC function. However, the precise alterations in ACC function that occur in response to regional inflammation, systemic inflammation and exposure to bacterial products have yet to be fully characterized. The present thesis was therefore performed to test the hypothesis that gastrointestinal (GI) and systemic inflammation modulate ACC Ca2+ signaling, and that ACCs possess the ability to directly detect microbe-associated molecular patterns (MAMPs).
Ca2+ signaling was assessed in single ACCs isolated from control mice and mice with GI or systemic inflammation using Ca2+ imaging and perforated patch clamp electrophysiology. Acute and chronic GI inflammation consistently reduced high-K+-stimulated Ca2+ transients in ACCs through an inhibition of voltage-gated Ca2+ current. In contrast, systemic inflammation significantly enhanced high-K+-stimulated Ca2+ transients and catecholamine secretion through an increase in Ca2+ release from the endoplasmic reticulum. Incubation of control ACCs in serum obtained from mice with systemic inflammation produced a similar increase in Ca2+ signaling, suggesting that circulating mediators play an important role in this response.
To determine whether ACCs can directly detect MAMPs, Ca2+ signaling, excitability and neurotransmitter release were assessed in control ACCs and ACCs incubated in media containing lipopolysaccharide (LPS). Unlike GI and systemic inflammation, LPS did not affect ACC Ca2+ signaling. However, LPS dose- and time-dependently hyperpolarized ACC resting membrane potential and enhanced large conductance Ca2+-activated K+ currents. Consistent with membrane hyperpolarization, LPS reduced ACC excitability and inhibited neuropeptide Y release. These effects were mediated by Toll-like receptor 4 and nuclear factor-κB.
In summary, GI and systemic inflammation produce opposite effects on ACC Ca2+ signaling through distinct mechanisms, and ACCs can directly detect MAMPs. These findings extend our knowledge of the complex integration performed by the immune system-nervous system network during health and disease. / Thesis (Ph.D, Physiology) -- Queen's University, 2013-08-20 17:15:23.945
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Involvement of Alpha1-adrenoceptors in the Cutaneous Blood Flow Increase Response to Sympathetic Nerve Stimulation in Rats with Chronic Constriction InjuryKoeda, Tomoko, Sato, Jun, Mizumura, Kazue 12 1900 (has links)
国立情報学研究所で電子化したコンテンツを使用している。
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Effectiveness of Centrifuge-induced Artificial Gravity with Ergometric Exercise as a Countermeasure during Simulated Microgravity Exposure in HumansIwase, Satoshi, Fu, Qi, Morimoto, Eiichi, Takada, Hiroki, Kamiya, Atsunori, Michikami, Daisaku, Kawanokuchi, Jun, Shiozawa, Tomoki, Hirayanagi, Kaname, Iwasaki, Ken-ichi, Yajima, Kazuyoshi, Mano, Tadaaki 12 1900 (has links)
国立情報学研究所で電子化したコンテンツを使用している。
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Microneurographic Analysis of Sympathetic Outflow to the Skin in Patients with Postoperative Hypothalamic Dysfunction after Suprasellar TumorsWATANABE, Tadashi, IWASE, Satoshi, SAITO, Kiyoshi, NAGATANI, Tetsuya, YOSHIDA, Jun 12 1900 (has links)
国立情報学研究所で電子化したコンテンツを使用している。
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Physiological Responses to Acute Global Hypoxia and their Relationship to Brain Injury In the Newborn Piglet: What are the Important Responses?Thomas Harris Unknown Date (has links)
Perinatal asphyxia is a significant contributor to neonatal brain injury. In the clinical environment there is variability in the severity of neural injury in neonates with similar clinical histories. Whilst the duration and intensity of hypoxia is well known to influence the severity of neurological outcome, the global physiological responses to hypoxia may also affect the subsequent variability in neurological outcome. The first step in this project was to identify which physiological response/s during a constant global hypoxic-ischemic insult influence the severity of neurological outcome in the newborn piglet and to assess the relative importance of these responses. Hypoxia/hypercapnia was induced in anaesthetized piglets by reducing the fraction of inspired oxygen to 0.1 (10%) and the ventilation rate from 30-10 breaths per minute for 45 minutes. Neurological outcome was determined by using functional markers including aEEG amplitude and cerebral impedance, and the structural marker microtubule associated protein-2 immunohistochemistry at 6 hours post hypoxia. The results from the initial study indicated that there was significant variability in neurological outcome following a constant hypoxia/hypercapnia insult. Serum cortisol concentrations were highly variable at the end of hypoxia (mean ± SD; 240.7 ± 90.9 nmol/L) and associated with cardiovascular function (time heart rate below baseline; r = 0.69) and neurological outcome (r = 0.70). Cardiovascular function (time heart rate was below baseline) and neurological outcome were strongly associated (r = 0.77). In this study we observed an oscillating pattern in cardiovascular function during hypoxia in some animals. In the regression analysis variability in cortisol concentrations and cardiovascular function explained 68% of the variability in the severity of neurological outcome. Additional physiological factors did not improve the strength of the association with neurological outcome. The variability in the physiological responses, particularly cardiovascular and endocrine responses to hypoxia may be more important determinants of neurological outcome then previously recognised. Results from the initial study opened up several questions about the relationship between cortisol and cardiovascular function during hypoxia and the relationship to the subsequent neurological outcome. Since variability in cortisol concentrations was associated with both cardiovascular function and neurological outcome the second step of this thesis was to investigate what factors contributed to the variability in serum cortisol concentrations during hypoxia. It is important to understand why some individuals produce more cortisol than others, and as a result are protected against brain injury. The aim was to determine if the variability in serum cortisol concentrations was the result of variability in ACTH concentrations during acute global hypoxia. The results from this study showed that early changes in serum cortisol concentration (15 minutes) were not correlated with ACTH (R2 = 0.26, P = 0.1), however, later changes (30 – 45 minutes) were (R2 0.45 - 0.68). This suggests that the primary factor controlling serum cortisol concentrations before hypoxia and during later hypoxia is ACTH concentrations. These data suggest that other factors may control cortisol secretion during early hypoxia; a key mechanism responsible for these changes may be the activity of the sympathetic nervous system and the maturity of the adrenal medullae. Since, higher cortisol concentrations were associated with better cardiovascular function and neurological outcome. As a result of this observation the aim of this study was to determine if cortisol concentrations during hypoxia are the causative factor responsible for improved cardiovascular function and better neurological outcome. The results from this study showed that manipulating serum cortisol concentrations into high (<500nmol/l) and low (>50nmol/l) levels during hypoxia did not affect cardiovascular function (P = 0.68) or neurological outcome (P = 46). Within each group (low, high and control hypoxia group) there was significant variability in cardiovascular function during hypoxia, which was associated with neurological outcome. (r = -0.63, p = 0.01). This study showed that serum cortisol concentrations during hypoxia are not the causative factor impacting on improved cardiovascular function and neurological outcome. It is possible that factors affecting both cardiovascular function and cortisol production such as activity of the sympathetic nervous system, may be a possible mechanism behind the variability in neurological outcome and cardiovascular function. Additionally, this study showed that cortisol concentrations at 3 hours post hypoxia were associated with neurological outcome (r = -0.67, p = 0.01). The animals with poorer outcome may also be those with greater multi-organ damage and thus reduced ability to clear cortisol from the systemic circulation. In light of this finding it may be interesting to assess cortisol concentration in the human neonate at 3 hours post hypoxia and determine the relationship to neurological outcome. In the final study of this thesis the function of the cardiovascular system during hypoxia was investigated in more detail because of its strong association with neurological outcome (results observed in Chapter 2 and 4. Few researchers have reported on oscillations in cardiovascular function, particularly type-3 waves, during hypoxia in the neonate. The aim of this study was to determine the characteristics and occurrence of type-3 waves in the neonatal piglet and their relationship to neurological outcome following acute global hypoxia. The result showed that the development of type-3 waves in cardiovascular function occurred in 56% of animals. An oscillating pattern was significantly associated with better neurological outcome (p = 0.01) and a lower duration of hypotension during hypoxia (p = 0.02), and occurred more frequently in females (p = 0.024). The development of type-3 waves during acute global hypoxia is a key mechanism in promoting natural tolerance; and may be the result of greater activity, maturity or sensitivity of the sympathetic nervous system in females compared to males. This may explain the improved neurological outcome following hypoxia in the female neonate seen in the clinical setting.
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Physiological Responses to Acute Global Hypoxia and their Relationship to Brain Injury In the Newborn Piglet: What are the Important Responses?Thomas Harris Unknown Date (has links)
Perinatal asphyxia is a significant contributor to neonatal brain injury. In the clinical environment there is variability in the severity of neural injury in neonates with similar clinical histories. Whilst the duration and intensity of hypoxia is well known to influence the severity of neurological outcome, the global physiological responses to hypoxia may also affect the subsequent variability in neurological outcome. The first step in this project was to identify which physiological response/s during a constant global hypoxic-ischemic insult influence the severity of neurological outcome in the newborn piglet and to assess the relative importance of these responses. Hypoxia/hypercapnia was induced in anaesthetized piglets by reducing the fraction of inspired oxygen to 0.1 (10%) and the ventilation rate from 30-10 breaths per minute for 45 minutes. Neurological outcome was determined by using functional markers including aEEG amplitude and cerebral impedance, and the structural marker microtubule associated protein-2 immunohistochemistry at 6 hours post hypoxia. The results from the initial study indicated that there was significant variability in neurological outcome following a constant hypoxia/hypercapnia insult. Serum cortisol concentrations were highly variable at the end of hypoxia (mean ± SD; 240.7 ± 90.9 nmol/L) and associated with cardiovascular function (time heart rate below baseline; r = 0.69) and neurological outcome (r = 0.70). Cardiovascular function (time heart rate was below baseline) and neurological outcome were strongly associated (r = 0.77). In this study we observed an oscillating pattern in cardiovascular function during hypoxia in some animals. In the regression analysis variability in cortisol concentrations and cardiovascular function explained 68% of the variability in the severity of neurological outcome. Additional physiological factors did not improve the strength of the association with neurological outcome. The variability in the physiological responses, particularly cardiovascular and endocrine responses to hypoxia may be more important determinants of neurological outcome then previously recognised. Results from the initial study opened up several questions about the relationship between cortisol and cardiovascular function during hypoxia and the relationship to the subsequent neurological outcome. Since variability in cortisol concentrations was associated with both cardiovascular function and neurological outcome the second step of this thesis was to investigate what factors contributed to the variability in serum cortisol concentrations during hypoxia. It is important to understand why some individuals produce more cortisol than others, and as a result are protected against brain injury. The aim was to determine if the variability in serum cortisol concentrations was the result of variability in ACTH concentrations during acute global hypoxia. The results from this study showed that early changes in serum cortisol concentration (15 minutes) were not correlated with ACTH (R2 = 0.26, P = 0.1), however, later changes (30 – 45 minutes) were (R2 0.45 - 0.68). This suggests that the primary factor controlling serum cortisol concentrations before hypoxia and during later hypoxia is ACTH concentrations. These data suggest that other factors may control cortisol secretion during early hypoxia; a key mechanism responsible for these changes may be the activity of the sympathetic nervous system and the maturity of the adrenal medullae. Since, higher cortisol concentrations were associated with better cardiovascular function and neurological outcome. As a result of this observation the aim of this study was to determine if cortisol concentrations during hypoxia are the causative factor responsible for improved cardiovascular function and better neurological outcome. The results from this study showed that manipulating serum cortisol concentrations into high (<500nmol/l) and low (>50nmol/l) levels during hypoxia did not affect cardiovascular function (P = 0.68) or neurological outcome (P = 46). Within each group (low, high and control hypoxia group) there was significant variability in cardiovascular function during hypoxia, which was associated with neurological outcome. (r = -0.63, p = 0.01). This study showed that serum cortisol concentrations during hypoxia are not the causative factor impacting on improved cardiovascular function and neurological outcome. It is possible that factors affecting both cardiovascular function and cortisol production such as activity of the sympathetic nervous system, may be a possible mechanism behind the variability in neurological outcome and cardiovascular function. Additionally, this study showed that cortisol concentrations at 3 hours post hypoxia were associated with neurological outcome (r = -0.67, p = 0.01). The animals with poorer outcome may also be those with greater multi-organ damage and thus reduced ability to clear cortisol from the systemic circulation. In light of this finding it may be interesting to assess cortisol concentration in the human neonate at 3 hours post hypoxia and determine the relationship to neurological outcome. In the final study of this thesis the function of the cardiovascular system during hypoxia was investigated in more detail because of its strong association with neurological outcome (results observed in Chapter 2 and 4. Few researchers have reported on oscillations in cardiovascular function, particularly type-3 waves, during hypoxia in the neonate. The aim of this study was to determine the characteristics and occurrence of type-3 waves in the neonatal piglet and their relationship to neurological outcome following acute global hypoxia. The result showed that the development of type-3 waves in cardiovascular function occurred in 56% of animals. An oscillating pattern was significantly associated with better neurological outcome (p = 0.01) and a lower duration of hypotension during hypoxia (p = 0.02), and occurred more frequently in females (p = 0.024). The development of type-3 waves during acute global hypoxia is a key mechanism in promoting natural tolerance; and may be the result of greater activity, maturity or sensitivity of the sympathetic nervous system in females compared to males. This may explain the improved neurological outcome following hypoxia in the female neonate seen in the clinical setting.
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A role of sympathetic nervous system in immunomodulation of early experimental African trypanosomiasis /Liu, Yajuan, January 2004 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.
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Zinc-finger transcription factors and the response of non-myelinating Schwann cells to axonal injuryEllerton, Elaine Louise, January 1900 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.
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