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Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Centre of Neuroscience. Title from pdf file main screen (viewed on April 18, 2010). Includes bibliographical references.

Thesis (Ph.D.)--Flinders University, Dept. of Human Physiology, Centre for Neuroscience. / Typescript bound. Includes bibliographical references: (leaves 187-191) Also available electronically via the World Wide Web.

Made available in DSpace on 2014-06-11T19:22:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-08-14Bitstream added on 2014-06-13T19:08:19Z : No. of bitstreams: 1 hoshi_ra_me_prud.pdf: 470187 bytes, checksum: 5cba677581b43beb6b7309e781ff9714 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O sistema nervoso autônomo (SNA) desempenha um papel importante na regulação dos processos fisiológicos do organismo humano tanto em condições normais quanto patológicas. Dentre as técnicas utilizadas para sua avaliação, a variabilidade da frequência cardíaca (VFC) tem emergido como uma medida simples e não-invasiva dos impulsos autonômicos, representando um dos mais promissores marcadores quantitativos do balanço autonômico. A VFC descreve as oscilações no intervalo entre batimentos cardíacos consecutivos (intervalos R-R), assim como oscilações entre frequências cardíacas instantâneas consecutivas. Trata-se de uma medida que pode ser utilizada para avaliar a modulação do SNA sob condições fisiológicas, tais como em situações de vigília e sono, diferentes posições do corpo, treinamento físico, e também em condições patológicas. Mudanças nos padrões da VFC fornecem um indicador sensível e antecipado de comprometimentos na saúde. Uma alta variabilidade na frequência cardíaca é sinal de boa adaptação, caracterizando um indivíduo saudável, com mecanismos autonômicos eficientes, enquanto que, baixa variabilidade é frequentemente um indicador de adaptação anormal e insuficiente do SNA, implicando a presença de mau funcionamento fisiológico no indivíduo. Diante da sua importância como um marcador que reflete a atividade do SNA sobre o nódulo sinusal e como uma ferramenta clínica para avaliar e identificar comprometimentos na saúde, este artigo revisa aspectos conceituais da VFC, dispositivos de mensuração, métodos de filtragem, índices utilizados para análise da VFC, limitações de utilização e aplicações clínicas da VFC. / Autonomic nervous system (ANS) plays an important role in the regulation of the physiological processes of the human organism during normal and pathological conditions. Among the techniques used in its evaluation, the heart rate variability (HRV) has arising as a simple and non-invasive measure of the autonomic impulses, representing one of the most promising quantitative markers of the autonomic balance. The HRV describes the oscillations in the interval between consecutive heart beats (RR interval), as well as the oscillations between consecutive instantaneous heart rates. It is a measure that can be used to assess the ANS modulation under physiological conditions, such as wakefulness and sleep conditions, different body positions, physical training and also pathological conditions. Changes in the HRV patterns provide a sensible and advanced indicator of health involvements. Higher HRV is a signal of good adaptation and characterizes a health person with efficient autonomic mechanisms, while lower HRV is frequently an indicator of abnormal and insufficient adaptation of the autonomic nervous system, provoking poor patient's physiological function. Because of its importance as a marker that reflects the ANS activity on the sinus node and as a clinical instrument to assess and identify health involvements, this study reviews conceptual aspects of the HRV, measurement devices, filtering methods, indexes used in the HRV analyses, limitations in the use and clinical applications of the HRV.

This thesis is broken into four chapters. The first two chapters summarize two separate lines of investigation into the role of a putative neurotoxin in the pathogenesis of Huntington's Disease (HD). The third chapter outlines an investigation of the putative role of beta-N-methylamino-L-alanine (BMAA) in the pathogenesis of amyotrophic lateral sclerosis (ALS), while the final chapter details a post-mortem investigation of the contents of biogenic amines and amino acids in the brain of a man who died of a familial form of parkinsonism. Chapter I is a description of a chromatographic technique developed to isolate quinolinic acid (QA), an endogenous compound implicated in the pathogenesis of HD, from deproteinized human sera. A cation exchange column was used to selectively isolate QA, which was eluted with 10 mM HCl. The eluted fractions were analyzed by UV spectrometry to isolate and quantify QA. Once the fractions corresponding the elution of authentic QA were isolated, concentrated and the excess HCl removed, the fractions were added to growing fetal rat striatal explant cultures as an assay of neurotoxicity. Since HD involves the selective degeneration of GABAergic neurons in the striatum, the activity of glutamic acid decarboxylase, the final enzyme in the synthesis of GABA, was used to determine the viability of the cultures. Unfortunately, the method was confounded by the contamination of all effluents by compounds originating from the cation exchange resin, which were discovered to be neurotoxic to the striatal cultures, and as a result the investigation had to be abandoned. Chapter II describes an investigation designed to further characterize the nature of neurotoxicity observed in the sera obtained from patients with HD (Perry et al. 1987). Compounds with the capacity to selectively stimulate neurons at the N-methyl-D-aspartate (NMDA) receptor have been implicated in a variety of neurodegenerative disorders, including HD. Selective antagonists at the NMDA receptor have been shown to protect neurons from the degenerative effects of such "excitotoxins". The investigation described used MK-801, a potent noncompetitive NMDA antagonist, in an attempt to protect fetal rat striatal cultures from the neurodegenerative effects of the sera obtained from HD patients. The results obtained were equivocal. No evidence was obtained to support a role of the NMDA receptor in the mediation of the neurotoxicity, and in addition the neurodegenerative effects of HD sera were not reproduced in the present investigation. A variety of possible explanations for the apparent discrepancy are suggested. Chapter III describes an experiment intended to produce an animal model of ALS based on the observations by Spencer et al. 1987 that chronic oral administration of BMAA in monkeys produced the histological and behavioural characteristics of this disease. In the present investigation synthetic D,L-BMAA was given by gavage to mice over an eleven week period. Since BMAA is known to act at the NMDA receptor, a subset of the mice were also given MK-801 in an effort to protect them from any deleterious effects based on the action of BMAA at this receptor. The animals were sacrificed at the end of the experiment, and biochemical analyses were performed on the striata and cortices of the animals. In addition, neuropathological studies were performed on the spinal cords, basal ganglia and related structures. The results indicated no biochemical or neuropathological abnormality as a result of BMAA administration. Chapter IV describes a post-mortem investigation of a man who was a member of a well described pedigree which carries an autosomal dominant form of parkinsonism. The object of the investigation was to determine post-mortem levels of dopamine, noradrenaline, serotonin and their metabolites, in addition to amino acids in various regions of brain. Although conflicting evidence was obtained during life, neuropathological findings and the present neurochemical analyses confirm the degeneration of the nigrostriatal dopaminergic tract, characteristic of parkinsonism, in this man. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

After dendrite transection, two primary injury current pathways may acount for cell death: (1) the lesion current at the site of injury and (2) the voltage sensitive calcium channels along the dendrite. Lesions were made with a laser microbeam in mouse spinal monolayer cell cultures. Polylysine was tried as a positively charged "molecular bandage" to block the lesion current. The calcium channel blockers, verapamil and nifedipine, were used to reduce the calcium channel current. Control toxicity curves were obtained for all three compounds. The results show that neither verapamil, nifedipine, nor polylysine (MW: 3,300) protect nerve cells after dendrite amputation 100 ptm from the soma. The data also indicate that these compounds do not slow the process of cell death after such physical trauma.

Autonomic nervous system activity is related to body weight regulation. Based on the MONA LISA hypothesis it has been suggested that most obese subjects and animals have low sympathetic nervous system activity. The aim of this study was to investigate whether there are differences in autonomic nervous system activity between lines of chickens selected for either high (HWS) or low body weight (LWS). In Exp. 1, various pharmacological agents were injected intravenously, and the changes in blood pressure (BP) and heart rate (HR) of both HWS and LWS chickens were compared. The results showed that the HWS birds had a greater increase in BP and HR than the LWS following injection of atropine, a muscarinic receptor blocker, and LWS birds had a greater decrease in BP and HR to propranolol, a beta- adrenergic receptor blocker than the HWS birds. These results suggested that HWS chickens have higher parasympathetic tone, whereas LWS chickens have a higher sympathetic nervous system tone regulating the cardiovascular system. HWS and LWS chickens displayed a similar response in BP and HR following injection of the ganglion blocker tetraethylammonium chloride. These results suggest that there is no significant difference in the central autonomic nervous system in the cardiovascular regulation between HWS and LWS together. Since there does not appear to be any differences in the activity of the autonomic nervous system activity at the level of the central nervous system, these findings imply that the difference in response to atropine and propranolol could be caused by differences in adrenal activity. The ratio of heart rate and blood pressure after the injection of phenylephrine showed significant difference between these two lines of birds, but not when phenylephrine was injected following atropine. This result indicated that HWS are more dependent on the parasympathetic nervous system to regulate the baroreceptor reflex. The percentage of adrenal and sympathetic impact on the regulation of heart rate showed that LWS females required greater adrenal activity than the other birds. In Exp. 2, the body weight and food intake responses of HWS and LWS chickens to ip injections of reserpine were compared. Reserpine caused a transitory decrease in food intake and body weight in both lines of birds. However HWS chickens recovered more slowly from the depression caused by reserpine than the LWS chickens. This could be due to lower sympathetic nervous system activity. In conclusion, it appears that HWS may have lower sympathetic activity than LWS. Combining the results of both experiments, it appears that the HWS birds have lower sympathetic and higher parasympathetic activity. Furthermore central nervous system autonomic activity in BP and HR regulation is not different between HWS and LWS, but the activity of the adrenal gland may be different between these two lines of birds. / Master of Science

published_or_final_version / Anatomy / Master / Master of Philosophy

Orientador: Carlos Marcelo Pastre / Banca: Luiz Carlos Marques Vanderlei / Banca: Moacir Fernandes de Godoy / Resumo: O sistema nervoso autônomo (SNA) desempenha um papel importante na regulação dos processos fisiológicos do organismo humano tanto em condições normais quanto patológicas. Dentre as técnicas utilizadas para sua avaliação, a variabilidade da frequência cardíaca (VFC) tem emergido como uma medida simples e não-invasiva dos impulsos autonômicos, representando um dos mais promissores marcadores quantitativos do balanço autonômico. A VFC descreve as oscilações no intervalo entre batimentos cardíacos consecutivos (intervalos R-R), assim como oscilações entre frequências cardíacas instantâneas consecutivas. Trata-se de uma medida que pode ser utilizada para avaliar a modulação do SNA sob condições fisiológicas, tais como em situações de vigília e sono, diferentes posições do corpo, treinamento físico, e também em condições patológicas. Mudanças nos padrões da VFC fornecem um indicador sensível e antecipado de comprometimentos na saúde. Uma alta variabilidade na frequência cardíaca é sinal de boa adaptação, caracterizando um indivíduo saudável, com mecanismos autonômicos eficientes, enquanto que, baixa variabilidade é frequentemente um indicador de adaptação anormal e insuficiente do SNA, implicando a presença de mau funcionamento fisiológico no indivíduo. Diante da sua importância como um marcador que reflete a atividade do SNA sobre o nódulo sinusal e como uma ferramenta clínica para avaliar e identificar comprometimentos na saúde, este artigo revisa aspectos conceituais da VFC, dispositivos de mensuração, métodos de filtragem, índices utilizados para análise da VFC, limitações de utilização e aplicações clínicas da VFC. / Abstract: Autonomic nervous system (ANS) plays an important role in the regulation of the physiological processes of the human organism during normal and pathological conditions. Among the techniques used in its evaluation, the heart rate variability (HRV) has arising as a simple and non-invasive measure of the autonomic impulses, representing one of the most promising quantitative markers of the autonomic balance. The HRV describes the oscillations in the interval between consecutive heart beats (RR interval), as well as the oscillations between consecutive instantaneous heart rates. It is a measure that can be used to assess the ANS modulation under physiological conditions, such as wakefulness and sleep conditions, different body positions, physical training and also pathological conditions. Changes in the HRV patterns provide a sensible and advanced indicator of health involvements. Higher HRV is a signal of good adaptation and characterizes a health person with efficient autonomic mechanisms, while lower HRV is frequently an indicator of abnormal and insufficient adaptation of the autonomic nervous system, provoking poor patient's physiological function. Because of its importance as a marker that reflects the ANS activity on the sinus node and as a clinical instrument to assess and identify health involvements, this study reviews conceptual aspects of the HRV, measurement devices, filtering methods, indexes used in the HRV analyses, limitations in the use and clinical applications of the HRV. / Mestre

The goal of this study was to build on the historic use of the avian model of development and also to further the knowledge of autonomic nervous system (ANS) regulation of cardiovascular function in vertebrates. Vasoactive drugs sodium nitroprusside, a vasodilator and phenylephrine, a vasoconstrictor were used to study the correlation of cardiovascular function relationship with nerve activity, both sympathetic and parasympathetic (vagal). Additionally, ANG II was used to assess its effects on vagal inhibition. The present study shows that pharmacologically-induced hypertension is associated with a fall in mSNA, indicating that the capacity for sympathetic autonomic cardiovascular regulation is established by late incubation however, late-stage embryonic chickens did not show a significant increase in mSNA during hypotension. The hypotensive response of the embryo was not accompanied by the expected inhibition of vagal discharge; however a slight but insignificant reduction in vagal discharge was noted. When vagal efferent output was isolated, a significant drop in vagal efferent activity was noted in response to hypotension. The present study showed late-stage embryonic chickens lack a vagal response to hypertension in both efferent and sensory limbs. In this study, vagal discharge was reduced from baseline levels in response to Ang II. Collectively, the present study indicates that the lack of a decreased heart rate, in response to increases in Pm caused by Ang II, is due to a central inhibitory action of Ang II on the vagus. Data from the present study suggests that although autonomic interaction with the cardiovascular system in present in late-stage chicken embryos, it is still underdeveloped and possesses a limited capacity.