O câncer de mama é o tipo de câncer que mais acomete as mulheres e a principal causa de morte na faixa entre 40 e 55 anos. Apesar de apresentar variação internacional, suas taxas seguem aumentando mundialmente, sendo até cinco vezes mais frequente em países desenvolvidos. A industrialização gera aumento da exposição à luz durante a noite, o que causa supressão de melatonina. A melatonina é o principal hormônio secretado pela glândula pineal e possui atividade oncostática e antioxidante, interfere no controle do ciclo celular, função imunológica e nos hormônios esteróides. O objetivo desta dissertação e apresentar o racional e o desenvolvimento do estudo cujo objetivo foi avaliar o efeito da terapia com melatonina sobre o desenvolvimento de tumores mamários em ratas expostas ou não a dessincronização circadiana. A indução da carcinogênese mamária foi através de administração intragástrica de DMBA em 39 ratas Sprague-dawley entre 41 e 46 dias. Os animais foram randomizados em 04 grupos, Sincronizados sem tratamento, Dessincronizados sem tratamento, Sincronizados com melatonina e Dessincronizados com melatonina. Os grupos Sincronizados foram mantidos em ciclo claro/escuro de 12/12 horas e os dessincronizados a ciclo claro/escuro de 11/11 horas, durante 8 semanas. O desenvolvimento tumoral ocorreu em 32 animais (82,05%), totalizando 73 tumores. A melatonina apresentou efeitos benéficos quanto a multiplicidade tumoral, grau histológico, tamanho dos tumores e peso dos animais, enquanto que a dessincronização não interferiu de forma significativa na carcinogênese mamária. / Breast cancer is the type of cancer that most affects women and the leading cause of death in the age between 40 and 55 years. Despite presenting international variation, their rates continue to increase worldwide, with up to five times more common in developed countries. The industrialization generates increased exposure to light at night, which causes suppression of melatonin. Melatonin is the main hormone secreted by the pineal gland and has oncostatic and antioxidant activity, interferes with cell cycle control, immune function and steroid hormones. The aim of this dissertation and present the rationale and development of the study whose objective was to evaluate the effect of melatonin therapy on the development of mammary tumors in rats exposed or not the circadian desynchronization. Induction of mammary carcinogenesis was via intragastric administration of DMBA in 39 Sprague- Dawley rats between 41 and 46 days. The animals were randomized into 04 groups, Synchronized and untreated, desynchronized and untreated, synchronized and with melatonin, desynchronized and with melatonin. Synchronized Groups were kept in a light / dark cycle of 12/12 hours and the desynchronized in a light / dark cycle of 11/11 hours for 8 weeks. The tumor development occurred in 32 animals (82.05%), totaling 73 tumors. Melatonin showed beneficial effects on tumor multiplicity, histological grade, tumor size and weight of the animals, while desynchronization did not interfere significantly in breast carcinogenesis.

There is a need for improved understanding of interactions between electromagnetic fields and biological tissues. In this thesis, the effects of exposure to 50 Hz magnetic fields, associated with power generation and use, and 1800 MHz fields associated with mobile phones were investigated with particular focus on the plastic processes that are involved in cognitive function. After repeated, daily exposure of young adult C57Bl/6J mice to an 1800 MHz field at 3 W/kg, very subtle changes in expression of genes involved in synaptic plasticity were found (p < 0.05). Spatial memory as measured in the water maze was not significantly affected by exposure. Exposure at 0.3 W/kg did not significantly affect any of the endpoints (p > 0.05). Indications of a greater sensitivity to exposure at 3 W/kg were seen in a senescence accelerated prone mouse model (SAMP8) compared to a resistant strain (SAMR1). However, only subtle effects of exposure were seen. Exposure of young C57Bl/6J mice to a 50 Hz field at 100 or 300 μT induced small but significant changes in expression in synaptic plasticity related genes (p < 0.05). Furthermore, repeated exposure significantly increased microglial density in the dorsal hippocampus (p < 0.05) and slightly decreased proliferation in the dorsal hippocampus (100 μT, p < 0.05). Spatial memory was not significantly affected by exposure. Acute exposure to a 50 Hz magnetic field for 30 minutes at 300 or 580 μT did not affect the adrenal response to a nocturnal white or blue light shock, while exposure at 580 μT in the absence of light significantly decreased per1 expression in the adrenal glands (p < 0.05), but not in the liver or dorsal hippocampus. Exposure at 580 μT for 24 hours had only minor transient effects on the rhythmic expression of the core clock genes. In summary, exposure to 50 Hz or 1800 MHz fields caused subtle and transient changes to some molecular mechanisms and cells involved in cognitive function and circadian rhythm control.

O câncer de mama é o tipo de câncer que mais acomete as mulheres e a principal causa de morte na faixa entre 40 e 55 anos. Apesar de apresentar variação internacional, suas taxas seguem aumentando mundialmente, sendo até cinco vezes mais frequente em países desenvolvidos. A industrialização gera aumento da exposição à luz durante a noite, o que causa supressão de melatonina. A melatonina é o principal hormônio secretado pela glândula pineal e possui atividade oncostática e antioxidante, interfere no controle do ciclo celular, função imunológica e nos hormônios esteróides. O objetivo desta dissertação e apresentar o racional e o desenvolvimento do estudo cujo objetivo foi avaliar o efeito da terapia com melatonina sobre o desenvolvimento de tumores mamários em ratas expostas ou não a dessincronização circadiana. A indução da carcinogênese mamária foi através de administração intragástrica de DMBA em 39 ratas Sprague-dawley entre 41 e 46 dias. Os animais foram randomizados em 04 grupos, Sincronizados sem tratamento, Dessincronizados sem tratamento, Sincronizados com melatonina e Dessincronizados com melatonina. Os grupos Sincronizados foram mantidos em ciclo claro/escuro de 12/12 horas e os dessincronizados a ciclo claro/escuro de 11/11 horas, durante 8 semanas. O desenvolvimento tumoral ocorreu em 32 animais (82,05%), totalizando 73 tumores. A melatonina apresentou efeitos benéficos quanto a multiplicidade tumoral, grau histológico, tamanho dos tumores e peso dos animais, enquanto que a dessincronização não interferiu de forma significativa na carcinogênese mamária. / Breast cancer is the type of cancer that most affects women and the leading cause of death in the age between 40 and 55 years. Despite presenting international variation, their rates continue to increase worldwide, with up to five times more common in developed countries. The industrialization generates increased exposure to light at night, which causes suppression of melatonin. Melatonin is the main hormone secreted by the pineal gland and has oncostatic and antioxidant activity, interferes with cell cycle control, immune function and steroid hormones. The aim of this dissertation and present the rationale and development of the study whose objective was to evaluate the effect of melatonin therapy on the development of mammary tumors in rats exposed or not the circadian desynchronization. Induction of mammary carcinogenesis was via intragastric administration of DMBA in 39 Sprague- Dawley rats between 41 and 46 days. The animals were randomized into 04 groups, Synchronized and untreated, desynchronized and untreated, synchronized and with melatonin, desynchronized and with melatonin. Synchronized Groups were kept in a light / dark cycle of 12/12 hours and the desynchronized in a light / dark cycle of 11/11 hours for 8 weeks. The tumor development occurred in 32 animals (82.05%), totaling 73 tumors. Melatonin showed beneficial effects on tumor multiplicity, histological grade, tumor size and weight of the animals, while desynchronization did not interfere significantly in breast carcinogenesis.

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / A sÃndrome alimentar noturna (SAN) à um distÃrbio alimentar caracterizada por um atraso no ritmo circadiano de apetite-saciedade, com ingestÃo calÃrica &#8805; 25% do total diÃrio apÃs a refeiÃÃo da noite e / ou pelo menos trÃs despertares noturnos acompanhados de alimentaÃÃo por semana. O Night Eating à um instrumento, que contÃm 14 itens com cinco pontos, usado como triagem para o diagnÃstico da SAN. O principal objetivo deste estudo foi traduzir para o portuguÃs a versÃo em inglÃs, atualizada, do Night Eating Questionnaire e adaptÃ-la culturalmente para uso em pacientes brasileiros. Na primeira etapa do estudo, foi realizada traduÃÃo; retrotraduÃÃo para o InglÃs; revisÃo das traduÃÃes e avaliaÃÃo da equivalÃncia semÃntica. Em seguida, avaliou-se a reprodutibilidade intra e interobservador num grupo de 37 indivÃduos. A confiabilidade do questionÃrio foi avaliada pelo coeficiente de Cronbach em 90 indivÃduos. A escala brasileira apresentou excelente consistÃncia interna, com coeficiente alfa ligeiramente inferior a 0,9. A escala traduzida e adaptada apresentou ainda adequada reprodutibilidade intra-observador com coeficientes entre 0,95 e 1,0 e interobservador com coeficientes entre 0,92 e 1,0. Estes resultados mostram que o instrumento traduzido tem clareza e que conduz a respostas consistentes, que nÃo se confundem com o passar do tempo. Desse modo, ficam estabelecidas a equivalÃncia conceitual dos itens e a equivalÃncia operacional das versÃes em portuguÃs e inglÃs. Novos estudos da aplicabilidade da versÃo brasileira utilizando amostras estratificadas por escolaridade, faixa de renda e classe social deverÃo ser realizados para avaliar este instrumento de forma mais precisa. / Night eating syndrome (NES) is an eating disorder characterized by a delay in the circadian time of food intake, with more than 25% of daily caloric intake after the evening meal or at least 3 nocturnal awakenings with ingestion per week. The Night Eating Questionnaire (NEQ) has 14 items with a 5 point scale and has been used as a tool for NES evaluation. The main objective of this study was to translate the current English version of the NEQ into Portuguese and adapting to cultural differences to allow for its use in Brazilian patients. The first part of the study consisted of translation; back-translation to English; review of the translations and evaluation of semantic equivalence. After this initial phase, intra and inter-observer reproducibility was assessed in a group of 37 individuals. The reliability of the questionnaire was evaluated by the Cronbach coefficient in 90 individuals. The translated and adapted version showed excellent internal consistency, with an alfa coefficient slightly below 0.9. This new version also had adequate reproducibility both intra-observer, with coefficients between 0.95 and 1.0, and inter-observer, with coefficients between 0.92 and 1.0. These results show that the translated questionnaire is clear, and the answers elicited are consistent and remain stable over time. Therefore, equivalence of the concepts in each item and operational equivalence of the English and Portuguese versions are established. Future studies evaluating the applicability of the Brazilian version using samples stratified by schooling, income and social status are necessary for a more precise evaluation of this tool.

O sistema circadiano das aves é composto pela retina, a região homóloga aos núcleos supraquiasmáticos de mamíferos (NSQ) e a glândula pineal. A retina apresenta muitos eventos fisiológicos rítmicos, como por exemplo os movimentos das células fotorreceptoras em vertebrados não mamíferos, a expressão de opsinas, regeneração do cromóforo visual e produção e liberação de melatonina e dopamina. Todos estes eventos rítmicos são coordenados para prever alterações nas condições luminosas que ocorrem durante o dia, otimizando a função retiniana. Neste trabalho foi investigada a expressão de componentes chave de um sistema circadiano, incluindo os dois genes de melanopsina, Opn4x e Opn4m, os genes de relógio Clock e Per2, e os genes das enzimas chave da síntese de melatonina, N-Acetiltransferase, e de dopamina, Tirosina Hidroxilase, em células da retina de embriões de galinha. Culturas primárias de retina de embriões de galinha com 8 dias foram preparadas no ZT0 (quando as luz é acesa) e semeadas na densidade de 107 células por frasco de 25 cm2 . As células foram mantidas em ambiente úmido, com 5% CO2, a 40o C, em escuro constante, fotoperíodo 12C:12E, fotoperíodo 12C:12E seguido de escuro constante, ou em escuro constante na presença e na ausência de glutamato 100 &#956;M por 12 h. A extração de RNA total foi feita ao longo de 24 horas com intervalo de três horas tendo início no ZT0 do sexto dia. As amostras foram submetidas a RT-PCR seguido de PCR quantitativo para a quantificação de RNAm. Para confirmar a expressão da proteína OPN4x foi realizado ensaio imunohistoquímico com anticorpos anti-melanopsina de galinha desenvolvidos em coelho. Também foi feita a quantificação da concentração das proteínas OPN4x, CLOCK e TIROSINA HIDROXILASE através da técnica de Western Blot. A quantificação do RNAm em escuro constante não apresentou ritmos de transcrição para nenhum gene. Já as células mantidas em fotoperíodo 12C:12E apresentaram padrões rítmicos de transcrição para Clock, Per2, Opn4m, N-Acetiltransferase e Tirosina Hidroxilase. Glutamato 100 &#956;M foi eficaz em induzir ritmo em Clock, e inibiu drasticamente a expressão de Tirosina Hidroxilase e, apenas mais pontualmente, de Opn4x e Opn4m. Ensaios de viabilidade celular e fragmentação de DNA por citometria de fluxo demonstraram que essa inibição não foi resultante de ação tóxica ou apoptótica do glutamato. O neurotransmissor não teve qualquer efeito sobre a transcrição de Per2 e de N-Acetiltransferase. A quantificação protéica não indicou a presença de ritmo para CLOCK, OPN4x ou TIROSINA HIDROXILASE. A grande variabilidade inter-ensaios nos resultados de quantificação protéica sugere uma menor sensibilidade e precisão para esse método, quando comparado a PCR quantitativo. Nossos resultados indicam que as células de retina de embrião de 8 dias de galinha em cultura já contêm um relógio funcional, porém, este necessita do ciclo claro-escuro ou glutamato para sua sincronização. / The avian circadian system is composed by the retina, the mammalian homolog region of the supra-chiasmatic nucleus (SNC) and the pineal gland. The retina itself shows many rhythmic physiological events, such as movements of photoreceptor cells, opsin expression, retinaldehyde re-isomerization, melatonin and dopamine production and release. Altogether these rhythmic events are coordinated to predict environmental changes in light conditions during the day, optimizing retina function. In this work we investigated the expression of key components of a circadian system, including the two melanopsin genes, Opn4x, Opn4m, as well as the Clock, Per2, N-Acetyltransferase and Tyrosine Hidroxylase genes in chick embryo retinal cells. Primary cultures of chicken retina from 8-day-old embryos were prepared at ZT0 (lights on) and seeded at the density of 107 cells per 25 cm2 culture flask. The cells were kept in a humidified incubator in a 5% CO2 atmosphere at 40o C in constant dark, in 12L:12D, in 12L:12D followed by constant dark, or in constant dark in the absence or presence of 100 &#956;M glutamate for 12 h starting at ZT0 of the fifth day in vitro. Total RNA extraction was performed along 24 hours every three hours starting at ZT0 of the sixth day. The samples were submitted to RT-PCR followed by quantitative PCR for mRNA quantification. To analyze the Opn4x expression in these cells we performed an immunocytochemistry analysis with antibodies anti-chicken melanopsin developed in rabbit. We also quantified the protein levels of OPN4x, CLOCK AND TYROSINE HYDROXYLASE by Western Blot. The mRNA quantification showed no rhythm of transcription for any gene in cells kept in constant dark. However under a light-dark cycle, Clock, Per2, Opn4m, N-Acetyltransferase and Tyrosine Hydroxylase presented rhythm patterns of transcription. 100 &#956;M glutamate was able to induce rhythmic expression of Clock, and strongly inhibited the expression of Tyrosine Hydroxylase and, just punctually, of Opn4x and Opn4m. Assays of cell viability and DNA fragmentation using flow cytometry demonstrated that the inhibition did not result of glutamate toxic or apoptotic actions. The neurotransmitter had no effect on Per2 and N-Acetyltransferase transcription. Protein quantification by Western Blot showed no rhythmic oscillation of CLOCK, OPN4x or TYROSINE HYDROXYLASE. The great variability inter-assays seen in the results of protein quantification suggests that this method is less precise and sensitive than quantitative PCR. The present data show evidences that chicken embryonic retinal cells contain a functional circadian Clock. However light-dark cycle or glutamate stimuli are needed to its synchronization.

Orientador: Everardo Magalhães Carneiro / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-24T14:27:08Z (GMT). No. of bitstreams: 1 Borck_PatriciaCristine_M.pdf: 1384245 bytes, checksum: 89fa526347ae455e0cfcf6e3bd414018 (MD5) Previous issue date: 2014 / Resumo: Os processos fisiológicos como ciclo sono-vigília e o metabolismo estão sujeitos a oscilações circadianas e são regulados por um conjunto de genes conhecidos como genes do relógio, ou clock genes. Mutação nesses genes em camundongos reduz a secreção de insulina e a proliferação das células ? pancreáticas promovendo intolerância a glicose e hiperglicemia. Distúrbios nutricionais em fases iniciais da vida estão associados com o aparecimento do Diabetes Mellitus tipo 2 na vida adulta. Camundongos submetidos a restrição proteica intrauterina apresentam expressão alterada dos clock genes e maior suscetibilidade ao ganho de peso e intolerância a glicose. Neste trabalho tivemos como objetivo determinar a expressão diária dos clock genes em tecidos periféricos, hipotálamo e ilhotas pancreáticas de camundongos submetidos a restrição proteica. Avaliamos também o perfil oscilatório da secreção de insulina estimulada por glicose e pelo agonista colinérgico carbacol nesse modelo animal. Camundongos submetidos a restrição proteica (R) apresentaram características típicas de desnutrição como menor peso corpóreo, hipoinsulinemia, hipoproteinemia e maior tolerância a glicose e a insulina. Camundongos R apresentaram maior consumo alimentar, acompanhado de alterações no perfil oscilatório de genes hipotalâmicos Pomc (Pro-opiomelanocortina) e Npy (Neuropeptídeo Y). Nesse tecido, somente o gene do relógio Rev-erb? teve sua expressão influenciada pela restrição proteica. Camundongos R apresentaram, no fígado e músculo perda do perfil oscilatório para os genes Bmal1 e Clock. Ainda, no fígado e ilhotas pancreáticas a expressão de Rev-erb? foi alterada, com redução no conteúdo de mRNA. Em relação ao gene Per1, camundongos R exibiram adiantamento na expressão desse gene no tecido adiposo. No músculo e ilhotas houve perda da oscilação diária para esse gene. Camundongos R exibiram, no músculo e tecido adiposo, adiantamento na expressão do gene Per2. Ilhotas isoladas de camundongos controle (C) apresentaram padrão oscilatório de secreção de insulina sendo os maiores níveis atingido nos ZT 2 e 14 e redução no ZT 8. Contudo, camundongos R apresentaram redução na secreção de insulina estimulada por glicose, e perda do seu perfil oscilatório. O grupo R não apresentou alteração na liberação de insulina na presença do agonista e antagonista de Rev-erb?. Além disso, a expressão dos genes Sintaxina, Sinaptotagmina, e Insulina, estão reduzidos em camundongos R. O grupo R também apresentou perda oscilatória da secreção de insulina na presença de glicose associada ao Carbacol e redução na expressão do Receptor Muscarínico de Acetilcolina. Com os presentes resultados podemos concluir que camundongos submetidos a restrição proteica apresentaram características típicas de desnutrição com alteração na homeostase glicêmica e secreção de insulina. Ademais, camundongos R exibiram perda do perfil de secreção desse hormônio ao longo de 24 horas, o qual está relacionado com as alterações na expressão de Rev-erb?. Além disso, houve alteração no perfil de expressão dos genes clock, em especial Rev-erb?, Per1 e Per2 nos tecidos periféricos, fato que pode estar relacionado com as alterações na tolerância a glicose e insulina em camundongos R / Abstract: The physiological processes such as sleep-wake cycle and metabolism are subject to circadian fluctuations and are regulated by a group of genes known as clock genes or genes clock. Mutations in these genes in mice reduces insulin secretion and ?-pancreatic cell proliferation promoting impaired glucose tolerance and hyperglycemia. Nutritional disorders in the early stages of life are associated with the onset of type 2 diabetes in adulthood. Mice subjected to intrauterine protein restriction have altered expression of clock genes and increased susceptibility to weight gain and glucose intolerance. In this study we aimed to determine the daily expression of clock genes in peripheral tissues, hypothalamus and pancreatic islets of mice subjected to protein restriction. We also evaluated the oscillatory profile of the glucose stimulated insulin secretion and the cholinergic agonist carbachol in this animal model. Mice subjected to protein restriction (R) showed typical features of malnutrition as lower body weight , hypoinsulinemia , hypoproteinemia and increased glucose tolerance and insulin. R mice had higher food consumption, accompanied by changes in the oscillatory profile to Pomc and Npy gene in the hypothalamus. In this tissue, only the expression Rev- erb? gene was influenced by protein restriction. Mice R showed in the liver and muscle loss of the oscillatory profile to Clock and Bmal1 gene. Still, in liver and pancreatic islets the expression of Rev- erb? was changed, with reduction in mRNA content. Regarding the Per1 gene, R mice exhibited advance in the expression of this gene in adipose tissue. In muscle and islets there was loss of daily fluctuation for this gene. R mice exhibited, muscle and adipose tissue, in advance of Per2 gene expression. Islets isolated from control mice (C) showed oscillatory pattern of insulin secretion with the highest levels attained in the ZT 2 e 14 and reduction in the ZT 8. However, R mice had reduced glucose stimulated insulin secretion and loss of its oscillatory profile. R group showed no change in insulin release in the presence of Rev- erb? agonist and antagonist. Furthermore, the expression of Syntaxin, Synaptotagmin, and Insulin genes are reduced in R mice. R group also exhibited oscillatory loss of insulin secretion in the presence of glucose linked Carbachol and the reduction in the expression of Muscarinic Acetylcholine Receptor. With these results we can conclude that mice subjected to protein restriction showed typical features of malnutrition with alterations in glucose homeostasis and insulin secretion. Moreover, R mice exhibited loss of secretion of this hormone profile over 24 hours, which is associated with changes in the expression of Rev- erb?. In addition, there were changes in expression profile of clock genes, especially Rev-erb?, Per1 and Per2 in peripheral tissues, which may be related to changes in glucose tolerance and insulin in R mice / Mestrado / Fisiologia / Mestra em Biologia Funcional e Molecular

Sleep disturbance and behavioural difficulties are both prevalent problems in the intellectual and developmental disability population and can have a significant impact on quality of life for the individual and their family. This thesis investigated sleep, behaviour and circadian rhythm functioning in children with intellectual and developmental disabilities, and is presented in three sections. The first two papers have been prepared in accordance with the author guidelines of the journals proposed for submission, excluding tables and figures for ease of reading. The first paper is a systematic review of the literature examining the relationship between sleep disturbance and challenging behaviour in children with intellectual and developmental disabilities. 15 studies were included in the review and overall there were consistent findings of an association between the presence of sleep disruption and increased behavioural difficulties. A causal relationship could not be inferred due to the cross-sectional methodology of studies. Other factors, such as parental wellbeing, child level of intellectual disability and comorbidity of physical health conditions, need to be considered to understand the complexity of this relationship. Children with the neurodevelopmental disorder mucopolysaccharidosis type III (MPS III or Sanfilippo syndrome) present with high rates of sleep disturbance and challenging behaviour. The second paper investigates circadian rhythm functioning and activity levels in children with MPS III, compared to typically developing controls. Objective measurement of circadian rhythm and activity levels was obtained through actigraphic recording for 7-10 days. Children with MPS III had increased fragmentation of circadian rhythm, less stability of rhythm in relation to external cues and a differential pattern of activity across the day compared to controls. Overall, results were indicative of a disruption of circadian rhythm function in children with MPS III. The implications for clinical practice and future research are discussed. The third paper provides a critical appraisal of the overall research process, including further consideration of the strengths and limitations, implications for clinical practice, wider context of the research and personal reflections. An account of the project that was originally proposed with the MPS III population is also presented, alongside reflections on its termination.

The thesis presents a series of papers exploring catatonic symptoms and circadian rest-activity levels in autistic spectrum disorders (ASD). The thesis is presented in paper-based format and encompasses a literature review, an empirical paper and a critical appraisal. Paper 1 is a systematic review of available treatments for autistic catatonia. Catatonic symptoms are thought to occur in around 8% of young people with ASD, and it has been suggested that biological timing abnormalities may play a key role in the development of these difficulties. Twenty two papers were included in the final review, detailing treatment of a total of 28 cases of autistic catatonia. Both adult and paediatric cases were included. The range of treatments described encompassed electroconvulsive therapy, various psychotropic medications, behavioural and sensory therapies. The review highlights limitations in the available literature and suggests avenues for future research. Paper 2 explores circadian patterns in activity using actigraphy. A case series of 8 young people with an ASD diagnosis were recruited from specialist schools and asked to wear an actigraph for one week. Parents completed questionnaire measures of ASD traits and symptoms of autistic catatonia. Findings indicated a high degree of variability in circadian rest-activity cycles, both between participants and across the week. The study findings have implications for future research into circadian rest-activity levels in this population, as well as possible therapeutic applications. The final paper in the thesis presents a critical appraisal of the research, including discussion of strengths and limitations of the work, theoretical and clinical implications and directions for future research. Some personal reflections on the process of conducting the research are also included.

This study examines locomotor activity in samples of Frontinella pyramitela collected over its active season (April-October) to investigate whether seasonality and/or age may help explain the exceptional variability typically found in spider clock systems. Despite its noteworthy variability (%CV= 7.7), we have found that Frontinella has a mean free-running period of 28.4±2.18 hours that does not significantly vary over time. There is no correlation between day length and free-running period, indicating that varying length of FRP is not a function of photoperiod length. In LD 12:12 h, the window of activity is significantly smaller in April, gradually widening as the season continues, which may be evident of a shift in foraging strategy. Frontinella’s clock appears to mature before its entrainment mechanisms are fully developed, and towards the end of its season, there is strong evidence of circadian misalignment which may be a product of physiological age.

京都大学 / 新制・課程博士 / 博士(理学) / 甲第23042号 / 理博第4719号 / 新制||理||1676(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)教授 沼田 英治, 教授 曽田 貞滋, 准教授 森 哲 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM