Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)

Detalhes bibliográficos
Autor(a) principal: Lutte, Aline Haab
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
Texto Completo: http://tede2.pucrs.br/tede2/handle/tede/8406
Resumo: Ethanol is one of the most commonly used psychoactive substances with addictive properties in the world. One of the consequences to ethanol use is the Fetal Alcohol Syndrome (FAS), characterized by a set of changes in the development of children whose mothers ingested ethanol during gestation. Ethanol affects several neurotransmission systems, including the purinergic system. The embryonic development period is a phase of great susceptibility to exogenous and endogenous agents and the perturbations capable of altering the adenosinergic signaling during the embryonic phase may be related to morphological, biochemical and behavioral changes that go from birth to adult life. In recent years, a substantial number of evidence has emerged demonstrating that the synthesis and metabolism of purines and pyrimidines play important roles in controlling embryonic and fetal development and organogenesis. Dysfunctions in normal adenosine homeostasis during early brain development may have important consequences in the formation of neuronal circuits, thus contributing to neurodevelopmental changes. In the chapters that follow this thesis different mnemonic, biochemical and behavioral alterations in zebrafish exposed to ethanol were discussed in two distinct stages of development and the possible role of adenosine in such alterations. In the first chapter, the damage caused by ethanol in the gastrula / segmentation and pharyngula stages in the mnemonic parameters was analyzed, and suggests that the changes in the control of adenosine levels caused by ethanol could alter the neuromodulation of important components in memory formation, such as neurotransmitters. It was shown that adjustment of adenosine levels by the inhibition of ecto-5'-nucleotidase appears to be effective in restoring normal adenosine levels and memory acquisition in animals exposed to ethanol during pharyngula stage. A decrease in the body size of the animals in the proportional analysis of the telencephalon / encephalon and cerebellum / encephalon at both stages was detected when compared to controls. In the second chapter were evaluated the changes caused by ethanol exposition in the gastrula / segmentation and pharyngula stages in the ecto-5'-nucleotidase and adenosine deaminase enzymatic activity, gene expression of the enzyme ecto-5'-nucleotidase, morphological parameters and in the quantification of adenosine in zebrafish encephalon. Exposure to 1% ethanol did not promote severe morphological effects, but a decrease in body length was observed. The enzymatic activity of the ecto-5'-nucleotidase was increased in adult 9 animals exposed to ethanol in the gastrula / segmentation stage. The ecto-5'-nucleotidase gene expression and the enzymatic activity of adenosine deaminase did not change significantly at both stages of development. The adenosine quantification did not show differences in nucleoside concentration in total encephalon of adult animals exposed to ethanol at early development. In the third chapter, the behavioral parameters of locomotion, anxiety, aggressiveness and social interaction were evaluated in animals at 3 and 12 months after fertilization (mpf) that were exposed to1% ethanol during gastrula / segmentation and pharyngula stages. In addition, was evaluated the use of inhibitors of the enzymes ecto-5'-nucleotidase (3 and 12 mpf) and adenosine deaminase (3 mpf) on the behavioral changes investigated. There were no significant changes in locomotor parameters. An anxiolytic profile was detected at 3 mpf in the ethanol exposed animals at both stages of development, however, this profile did not remain at 12 mpf and the use of the inhibitors did not generate significant effects in this parameter. The aggressiveness had a significant increase in ethanol exposed animals at the pharyngula stage at 3 mpf and remained increased at 12 mpf, being recovered with the use of the ecto-5'-nucleotidase inhibitor. The social interaction decreased in the ethanol exposed animals in both stages of development at 3 mpf, being recovered by the use of the ecto-5'nucleotidase inhibitor in those animails exposed to ethanol in the pharyngula stage. At 12 mpf there were no significant changes. These results are in agreement with a series of studies that show the importance of adenosinergic signaling during development, as well as the deleterious effects of disturbances in this signaling pathway. The results of this thesis, in contribution to what is in the literature, indicate that the modulation of adenosinergic signaling, especially compensatory adjustments between ecto-5'-nucleotidase and nucleoside transporters, may be important targets of gestational exposure to ethanol.
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spelling Silva, Rosane Souza dahttp://lattes.cnpq.br/9755074017170793http://lattes.cnpq.br/1303792927538865Lutte, Aline Haab2019-01-11T16:45:07Z2018-11-01http://tede2.pucrs.br/tede2/handle/tede/8406Ethanol is one of the most commonly used psychoactive substances with addictive properties in the world. One of the consequences to ethanol use is the Fetal Alcohol Syndrome (FAS), characterized by a set of changes in the development of children whose mothers ingested ethanol during gestation. Ethanol affects several neurotransmission systems, including the purinergic system. The embryonic development period is a phase of great susceptibility to exogenous and endogenous agents and the perturbations capable of altering the adenosinergic signaling during the embryonic phase may be related to morphological, biochemical and behavioral changes that go from birth to adult life. In recent years, a substantial number of evidence has emerged demonstrating that the synthesis and metabolism of purines and pyrimidines play important roles in controlling embryonic and fetal development and organogenesis. Dysfunctions in normal adenosine homeostasis during early brain development may have important consequences in the formation of neuronal circuits, thus contributing to neurodevelopmental changes. In the chapters that follow this thesis different mnemonic, biochemical and behavioral alterations in zebrafish exposed to ethanol were discussed in two distinct stages of development and the possible role of adenosine in such alterations. In the first chapter, the damage caused by ethanol in the gastrula / segmentation and pharyngula stages in the mnemonic parameters was analyzed, and suggests that the changes in the control of adenosine levels caused by ethanol could alter the neuromodulation of important components in memory formation, such as neurotransmitters. It was shown that adjustment of adenosine levels by the inhibition of ecto-5'-nucleotidase appears to be effective in restoring normal adenosine levels and memory acquisition in animals exposed to ethanol during pharyngula stage. A decrease in the body size of the animals in the proportional analysis of the telencephalon / encephalon and cerebellum / encephalon at both stages was detected when compared to controls. In the second chapter were evaluated the changes caused by ethanol exposition in the gastrula / segmentation and pharyngula stages in the ecto-5'-nucleotidase and adenosine deaminase enzymatic activity, gene expression of the enzyme ecto-5'-nucleotidase, morphological parameters and in the quantification of adenosine in zebrafish encephalon. Exposure to 1% ethanol did not promote severe morphological effects, but a decrease in body length was observed. The enzymatic activity of the ecto-5'-nucleotidase was increased in adult 9 animals exposed to ethanol in the gastrula / segmentation stage. The ecto-5'-nucleotidase gene expression and the enzymatic activity of adenosine deaminase did not change significantly at both stages of development. The adenosine quantification did not show differences in nucleoside concentration in total encephalon of adult animals exposed to ethanol at early development. In the third chapter, the behavioral parameters of locomotion, anxiety, aggressiveness and social interaction were evaluated in animals at 3 and 12 months after fertilization (mpf) that were exposed to1% ethanol during gastrula / segmentation and pharyngula stages. In addition, was evaluated the use of inhibitors of the enzymes ecto-5'-nucleotidase (3 and 12 mpf) and adenosine deaminase (3 mpf) on the behavioral changes investigated. There were no significant changes in locomotor parameters. An anxiolytic profile was detected at 3 mpf in the ethanol exposed animals at both stages of development, however, this profile did not remain at 12 mpf and the use of the inhibitors did not generate significant effects in this parameter. The aggressiveness had a significant increase in ethanol exposed animals at the pharyngula stage at 3 mpf and remained increased at 12 mpf, being recovered with the use of the ecto-5'-nucleotidase inhibitor. The social interaction decreased in the ethanol exposed animals in both stages of development at 3 mpf, being recovered by the use of the ecto-5'nucleotidase inhibitor in those animails exposed to ethanol in the pharyngula stage. At 12 mpf there were no significant changes. These results are in agreement with a series of studies that show the importance of adenosinergic signaling during development, as well as the deleterious effects of disturbances in this signaling pathway. The results of this thesis, in contribution to what is in the literature, indicate that the modulation of adenosinergic signaling, especially compensatory adjustments between ecto-5'-nucleotidase and nucleoside transporters, may be important targets of gestational exposure to ethanol.O etanol é uma das substâncias psicoativas com propriedades que causam dependência mais comumente utilizadas no mundo. Uma das consequências do uso do etanol é a Síndrome Alcoólica Fetal (SAF), caracterizada por um conjunto de alterações no desenvolvimento de crianças cujas mães ingeriram etanol durante a gestação. O etanol afeta vários sistemas de neurotransmissão, incluindo o sistema purinérgico. O período de desenvolvimento embrionário é uma fase de grande suscetibilidade a agentes exógenos e endógenos e as perturbações capazes de alterar a sinalização adenosinérgica durante a fase embrionária podem estar relacionadas com alterações morfológicas, bioquímicas e comportamentais que vão do nascimento à vida adulta. Nos últimos anos, um substancial conjunto de evidências têm surgido, demonstrando que a síntese e o metabolismo das purinas e pirimidinas desempenham papéis importantes no controle do desenvolvimento embrionário e fetal e da organogênese. Disfunções na homeostase normal da adenosina durante o desenvolvimento inicial do cérebro podem ter consequências importantes na formação de circuitos neuronais, contribuindo assim para as alterações do neurodesenvolvimento. Nos capítulos que seguem nesta tese foram abordadas diferentes alterações mnemônicas, bioquímicas e comportamentais em peixes-zebra expostos ao etanol em dois estágios distintos de desenvolvimento e o possível papel da adenosina em tais alterações. No primeiro capítulo foi analisado o prejuízo causado pelo etanol nos estágios de gástrula / segmentação e faríngula em parâmetros mnemônicos, e sugere que alterações no controle dos níveis de adenosina causadas pelo etanol poderiam alterar a neuromodulação de componentes importantes na formação da memória, como os neurotransmissores. Foi mostrado que o ajuste dos níveis de adenosina pela inibição da ecto-5’-nucleotidase parece ser eficaz na restauração da aquisição de memória em animais expostos ao etanol durante a faríngula. Foi detectada uma diminuição no tamanho corporal dos animais e nas proporções do telencéfalo / encéfalo e cerebelo / encéfalo em ambos os estágios, quando comparado com os controles. No segundo capítulo foram avaliadas as alterações causadas pelo etanol nos estágios de gástrula / segmentação e faríngula na atividade enzimática das enzimas ecto-5´-nucleotidase e adenosina deaminase e expressão gênica da enzima ecto-5´-nucleotidase, em parâmetros morfológicos a na quantificação da adenosina em encéfalo total de peixe-zebra. A exposição ao etanol 1% não promoveu efeitos morfológicos severos, porém foi percebido uma dimunição no comprimento corporal. A atividade enzimática da ecto-5´-nucleotidase foi 7 aumentada em animais adultos expostos ao etanol no estágio de gástrula. A expressão gênica da ecto-5´-nucleotidase e a atividade enzimática da adenosina deaminase não sofreram alterações significativas em ambos os estágios de desenvolvimento. A quantificação da adenosina não mostrou diferenças na concentração do nucleosídeo em encéfalo total de animais adultos expostos ao etanol no início do desenvolvimento. No terceiro capítulo foram avaliados os parâmetros comportamentais de locomoção, ansiedade, agressividade e interação social em animais de 3 e 12 meses pós fertilização (mpf) que foram expostos ao etanol 1% durante os estágios de desenvolvimento da gástrula / segmentação e faríngula. Adicionalmente, avaliou-se o uso de inibidores das enzimas ecto-5´nucleotidase (3 e 12 mpf) e adenosina deaminase (3 mpf) sobre as alterações comportamentais investigadas. Não houve alterações significativas nos parâmetros locomotores. Um perfil ansiolítico foi detectado aos 3 mpf nos animais expostos ao etanol em ambos estágios de desenvolvimento, porém, este perfil não se manteve aos 12 mpf e o uso dos inibidores não gerou efeitos significativos neste parâmetro. A agressividade teve um aumento significativo em animais de 3 mpf expostos ao etanol no estágio de faríngula e manteve-se aumentada aos 12 mpf, sendo recuperada com o uso do inibidor da ecto-5´-nucleotidase. A interação social diminuiu nos animais de 3 mpf expostos ao etanol em ambos os estágios de desenvolvimento, sendo recuperada pelo uso do inibidor da ecto-5´-nucleotidase naqueles animais expostos ao etanol na fase de faríngula. Aos 12 mpf não houve alterações significativas. Esses resultados estão de acordo com uma série de estudos que reportam a importância da sinalização adenosinérgica durante o desenvolvimento, bem como os efeitos deletérios provenientes de perturbações nessa via de sinalização. Os resultados desta tese, em contribuição ao que há na literatura, indicam que a modulação da sinalização adenosinérgica, em especial ajustes compensatórios entre ecto-5´-nucleotidase e transportadores de nucleosídeos, podem ser alvos importantes da exposição gestacional ao etanol.Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2019-01-03T12:24:28Z No. of bitstreams: 1 ALINE_HAAB_LUTTE_TES.pdf: 7088871 bytes, checksum: f15937b4196dbb032ba567f34169167f (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2019-01-11T16:41:29Z (GMT) No. of bitstreams: 1 ALINE_HAAB_LUTTE_TES.pdf: 7088871 bytes, checksum: f15937b4196dbb032ba567f34169167f (MD5)Made available in DSpace on 2019-01-11T16:45:07Z (GMT). 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dc.title.por.fl_str_mv Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)
title Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)
spellingShingle Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)
Lutte, Aline Haab
Adenosina
Ecto-5´-nucleotidase
Etanol
Desenvolvimento
Peixe-zebra
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
title_short Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)
title_full Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)
title_fullStr Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)
title_full_unstemmed Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)
title_sort Avaliação da participação do metabolismo da adenosina nos efeitos tardios da exposição embrionária ao etanol em peixe-zebra (Danio rerio)
author Lutte, Aline Haab
author_facet Lutte, Aline Haab
author_role author
dc.contributor.advisor1.fl_str_mv Silva, Rosane Souza da
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9755074017170793
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/1303792927538865
dc.contributor.author.fl_str_mv Lutte, Aline Haab
contributor_str_mv Silva, Rosane Souza da
dc.subject.por.fl_str_mv Adenosina
Ecto-5´-nucleotidase
Etanol
Desenvolvimento
Peixe-zebra
topic Adenosina
Ecto-5´-nucleotidase
Etanol
Desenvolvimento
Peixe-zebra
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
description Ethanol is one of the most commonly used psychoactive substances with addictive properties in the world. One of the consequences to ethanol use is the Fetal Alcohol Syndrome (FAS), characterized by a set of changes in the development of children whose mothers ingested ethanol during gestation. Ethanol affects several neurotransmission systems, including the purinergic system. The embryonic development period is a phase of great susceptibility to exogenous and endogenous agents and the perturbations capable of altering the adenosinergic signaling during the embryonic phase may be related to morphological, biochemical and behavioral changes that go from birth to adult life. In recent years, a substantial number of evidence has emerged demonstrating that the synthesis and metabolism of purines and pyrimidines play important roles in controlling embryonic and fetal development and organogenesis. Dysfunctions in normal adenosine homeostasis during early brain development may have important consequences in the formation of neuronal circuits, thus contributing to neurodevelopmental changes. In the chapters that follow this thesis different mnemonic, biochemical and behavioral alterations in zebrafish exposed to ethanol were discussed in two distinct stages of development and the possible role of adenosine in such alterations. In the first chapter, the damage caused by ethanol in the gastrula / segmentation and pharyngula stages in the mnemonic parameters was analyzed, and suggests that the changes in the control of adenosine levels caused by ethanol could alter the neuromodulation of important components in memory formation, such as neurotransmitters. It was shown that adjustment of adenosine levels by the inhibition of ecto-5'-nucleotidase appears to be effective in restoring normal adenosine levels and memory acquisition in animals exposed to ethanol during pharyngula stage. A decrease in the body size of the animals in the proportional analysis of the telencephalon / encephalon and cerebellum / encephalon at both stages was detected when compared to controls. In the second chapter were evaluated the changes caused by ethanol exposition in the gastrula / segmentation and pharyngula stages in the ecto-5'-nucleotidase and adenosine deaminase enzymatic activity, gene expression of the enzyme ecto-5'-nucleotidase, morphological parameters and in the quantification of adenosine in zebrafish encephalon. Exposure to 1% ethanol did not promote severe morphological effects, but a decrease in body length was observed. The enzymatic activity of the ecto-5'-nucleotidase was increased in adult 9 animals exposed to ethanol in the gastrula / segmentation stage. The ecto-5'-nucleotidase gene expression and the enzymatic activity of adenosine deaminase did not change significantly at both stages of development. The adenosine quantification did not show differences in nucleoside concentration in total encephalon of adult animals exposed to ethanol at early development. In the third chapter, the behavioral parameters of locomotion, anxiety, aggressiveness and social interaction were evaluated in animals at 3 and 12 months after fertilization (mpf) that were exposed to1% ethanol during gastrula / segmentation and pharyngula stages. In addition, was evaluated the use of inhibitors of the enzymes ecto-5'-nucleotidase (3 and 12 mpf) and adenosine deaminase (3 mpf) on the behavioral changes investigated. There were no significant changes in locomotor parameters. An anxiolytic profile was detected at 3 mpf in the ethanol exposed animals at both stages of development, however, this profile did not remain at 12 mpf and the use of the inhibitors did not generate significant effects in this parameter. The aggressiveness had a significant increase in ethanol exposed animals at the pharyngula stage at 3 mpf and remained increased at 12 mpf, being recovered with the use of the ecto-5'-nucleotidase inhibitor. The social interaction decreased in the ethanol exposed animals in both stages of development at 3 mpf, being recovered by the use of the ecto-5'nucleotidase inhibitor in those animails exposed to ethanol in the pharyngula stage. At 12 mpf there were no significant changes. These results are in agreement with a series of studies that show the importance of adenosinergic signaling during development, as well as the deleterious effects of disturbances in this signaling pathway. The results of this thesis, in contribution to what is in the literature, indicate that the modulation of adenosinergic signaling, especially compensatory adjustments between ecto-5'-nucleotidase and nucleoside transporters, may be important targets of gestational exposure to ethanol.
publishDate 2018
dc.date.issued.fl_str_mv 2018-11-01
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