Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish
Ano de defesa: | 2020 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Pontif?cia Universidade Cat?lica do Rio Grande do Sul
|
Programa de Pós-Graduação: |
Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de
|
Departamento: |
Escola de Medicina
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede2.pucrs.br/tede2/handle/tede/9418 |
Resumo: | Methionine participates directly or indirectly in the formation of other amino acids, neurotransmitters and in methylation processes, ensuring the homeostasis of an organism. However, genetic causes, called innate metabolism errors, or non-genetic causes can increase plasma methionine levels, a condition known as hypermethioninemia. Consequently, myopathies, liver disease and neurological problems can arise, and even a transient increase can cause toxicological effects. In addition, given the role of methionine in epigenetic control processes, subsequent generation may also be affected. However, assessments of the effects of transient hypermethioninemia are scarce and the mechanisms underlying this pathology have not yet been explored. Thus, the aim of this study was to explore the effects of transient hypermethioninemia in zebrafish parents and their offspring. Morphological changes, heartbeat, survival and locomotion were evaluated in the offspring in the larval stage, while anxiety, aggression, social interaction and aversive memory were evaluated in the parents and in the offspring in the adult stage. The levels of neurotransmitters and amino acids and the oxidative profile have also been explored in parents exposed to methionine and their offspring. The results obtained demonstrate that an exposure to methionine has long-lasting neurotoxic effects, since after the removal of methionine the exposed animals showed a decrease in anxiety, a decrease in aggression, and memory deficits. Concomitant to this, the levels of carnitine, creatine, cysteine and epinephrine were altered and redox homeostasis impaired seen by decreased levels of catalase, superoxide dismutase and total thiol content. We also observed that a transient increase in methionine has transgenerational effects, since the offspring of the exposed parents was hyperactive in the larval stage and, in the adult stage, also showed a decrease in anxiety with increased levels of neurotransmitters and an altered oxidative profile with increase of DCF levels. Therefore, high levels of methionine, even if transient, can cause long-lasting behavioral and neurochemical changes with effects also observed in the subsequent generation. |
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Bonan, Carla Denisehttp://lattes.cnpq.br/8058052532279136Wyse, Angela Terezinha de Souza Wysehttp://lattes.cnpq.br/8178867411563243http://lattes.cnpq.br/7231160227932397Zanandrea, Rodrigo2020-11-20T17:34:50Z2020-03-23http://tede2.pucrs.br/tede2/handle/tede/9418Methionine participates directly or indirectly in the formation of other amino acids, neurotransmitters and in methylation processes, ensuring the homeostasis of an organism. However, genetic causes, called innate metabolism errors, or non-genetic causes can increase plasma methionine levels, a condition known as hypermethioninemia. Consequently, myopathies, liver disease and neurological problems can arise, and even a transient increase can cause toxicological effects. In addition, given the role of methionine in epigenetic control processes, subsequent generation may also be affected. However, assessments of the effects of transient hypermethioninemia are scarce and the mechanisms underlying this pathology have not yet been explored. Thus, the aim of this study was to explore the effects of transient hypermethioninemia in zebrafish parents and their offspring. Morphological changes, heartbeat, survival and locomotion were evaluated in the offspring in the larval stage, while anxiety, aggression, social interaction and aversive memory were evaluated in the parents and in the offspring in the adult stage. The levels of neurotransmitters and amino acids and the oxidative profile have also been explored in parents exposed to methionine and their offspring. The results obtained demonstrate that an exposure to methionine has long-lasting neurotoxic effects, since after the removal of methionine the exposed animals showed a decrease in anxiety, a decrease in aggression, and memory deficits. Concomitant to this, the levels of carnitine, creatine, cysteine and epinephrine were altered and redox homeostasis impaired seen by decreased levels of catalase, superoxide dismutase and total thiol content. We also observed that a transient increase in methionine has transgenerational effects, since the offspring of the exposed parents was hyperactive in the larval stage and, in the adult stage, also showed a decrease in anxiety with increased levels of neurotransmitters and an altered oxidative profile with increase of DCF levels. Therefore, high levels of methionine, even if transient, can cause long-lasting behavioral and neurochemical changes with effects also observed in the subsequent generation.A metionina participa direta ou indiretamente da forma??o de outros amino?cidos, neurotransmissores e em processos de metila??o, garantindo a homeostase de um organismo. Entretanto, causas gen?ticas, chamadas de erros inatos do metabolismo, ou causas n?o gen?ticas podem aumentar os n?veis de metionina plasm?ticos, patologia essa conhecida como hipermetioninemia. Consequentemente, miopatias, doen?as hep?ticas e problemas neurol?gicos podem surgir, e at? mesmo um aumento transit?rio ? capaz de causar efeitos toxicol?gicos. Al?m disso, dado o papel da metionina em processos de controle epigen?tico, a gera??o subsequente tamb?m pode ser afetada. Entretanto, as avalia??es dos efeitos de uma hipermetioninemia transit?ria s?o escassas e os mecanismos subjacentes a essa patologia ainda n?o foram explorados. Assim, o objetivo desse estudo foi explorar os efeitos de uma hipermetioninemia transit?ria em zebrafish pais e em sua prole. Altera??es morfol?gicas, batimentos card?acos, sobreviv?ncia e locomo??o foram avaliados na prole no est?gio larval, enquanto ansiedade, agressividade, intera??o social e a mem?ria aversiva foram avaliados nos pais e na prole no est?gio adulto. Os n?veis de neurotransmissores e amino?cidos e o perfil oxidativo tamb?m foram explorados em pais e nos filhos de pais expostos a metionina. Os resultados obtidos demonstram que uma exposi??o ? metionina possui efeitos neurot?xicos duradouros, uma vez que ap?s a retirada da metionina os animais expostos apresentaram uma diminui??o da ansiedade, diminui??o da agressividade, e problemas de mem?ria. Concomitante a isso, os n?veis de carnitina, creatina, ciste?na e epinefrina foram alterados e a homeostase redox prejudicada visto pela diminui??o dos n?veis de catalase, super-?xido dismutase e do conte?do de ti?is totais. Observamos tamb?m que um aumento transit?rio da metionina possui efeitos transgeracionais, pois a prole dos pais expostos, no est?gio larval, estava hiperativa, e no est?gio adulto tamb?m apresentou uma diminui??o da ansiedade, com aumento dos n?veis de neurotransmissores e um perfil oxidativo alterado com aumento dos n?veis de DCF. Portanto, os n?veis altos de metionina, mesmo que transit?rios, podem causar altera??es comportamentais e neuroqu?micas duradouras com efeitos tamb?m observados na gera??o subsequente.Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2020-07-27T16:46:27Z No. of bitstreams: 1 Dissertacao_Rodrigo_Zanandrea_versao_final.pdf: 3659414 bytes, checksum: 3c2bd014aab517e6797ebf803a527bf8 (MD5)Rejected by Clarissa Selbach (clarissa.selbach@pucrs.br), reason: Rejeitado o dep?sito da disserta??o de RODRIGO ZANANDREA por n?o constar palavras-chave no resumo e keywords no abstract. on 2020-10-23T18:47:14Z (GMT)Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2020-10-27T14:53:20Z No. of bitstreams: 1 Dissertacao_compl_versao_final_atualizada.pdf: 1287687 bytes, checksum: 7e78192253f64d9010eb3a618791c044 (MD5)Approved for entry into archive by Sarajane Pan (sarajane.pan@pucrs.br) on 2020-11-20T17:29:25Z (GMT) No. of bitstreams: 1 Dissertacao_compl_versao_final_atualizada.pdf: 1287687 bytes, checksum: 7e78192253f64d9010eb3a618791c044 (MD5)Made available in DSpace on 2020-11-20T17:34:50Z (GMT). No. of bitstreams: 1 Dissertacao_compl_versao_final_atualizada.pdf: 1287687 bytes, checksum: 7e78192253f64d9010eb3a618791c044 (MD5) Previous issue date: 2020-03-23Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPqapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/179586/DIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdf.jpgporPontif?cia Universidade Cat?lica do Rio Grande do SulPrograma de P?s-Gradua??o em Medicina e Ci?ncias da Sa?dePUCRSBrasilEscola de MedicinaHipermetioninemiaMetioninaEstresse OxidativoZebrafishTransgeracionalHypermethioninemiaMethionineOxidative StressZebrafishTransgenerationalCIENCIAS DA SAUDE::MEDICINAExposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafishinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTrabalho ser? publicado como artigo ou livro60 meses20/11/2025-721401722658532398500500500600-224747486637135387-9693694523087866271802873727776104890info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILDIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdf.jpgDIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdf.jpgimage/jpeg4088http://tede2.pucrs.br/tede2/bitstream/tede/9418/6/DIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdf.jpg2e02006e86e27df1e8668c98bd09471bMD56TEXTDIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdf.txtDIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdf.txttext/plain2330http://tede2.pucrs.br/tede2/bitstream/tede/9418/5/DIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdf.txt78b67fc32c0d84b401edf4addd4add2aMD55ORIGINALDIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdfDIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdfapplication/pdf432959http://tede2.pucrs.br/tede2/bitstream/tede/9418/4/DIS_RODRIGO_ZANANDREA_CONFIDENCIAL.pdfde8b1e8065f9ecf23d9253dfb67f57faMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-8590http://tede2.pucrs.br/tede2/bitstream/tede/9418/3/license.txt220e11f2d3ba5354f917c7035aadef24MD53tede/94182020-11-20 20:00:11.151oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2020-11-20T22:00:11Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish |
title |
Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish |
spellingShingle |
Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish Zanandrea, Rodrigo Hipermetioninemia Metionina Estresse Oxidativo Zebrafish Transgeracional Hypermethioninemia Methionine Oxidative Stress Zebrafish Transgenerational CIENCIAS DA SAUDE::MEDICINA |
title_short |
Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish |
title_full |
Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish |
title_fullStr |
Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish |
title_full_unstemmed |
Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish |
title_sort |
Exposi??o parental transit?ria ? metionina : avalia??o de par?metros comportamentais e neuroqu?micos em pais e prole de zebrafish |
author |
Zanandrea, Rodrigo |
author_facet |
Zanandrea, Rodrigo |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bonan, Carla Denise |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8058052532279136 |
dc.contributor.advisor-co1.fl_str_mv |
Wyse, Angela Terezinha de Souza Wyse |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/8178867411563243 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/7231160227932397 |
dc.contributor.author.fl_str_mv |
Zanandrea, Rodrigo |
contributor_str_mv |
Bonan, Carla Denise Wyse, Angela Terezinha de Souza Wyse |
dc.subject.por.fl_str_mv |
Hipermetioninemia Metionina Estresse Oxidativo Zebrafish Transgeracional |
topic |
Hipermetioninemia Metionina Estresse Oxidativo Zebrafish Transgeracional Hypermethioninemia Methionine Oxidative Stress Zebrafish Transgenerational CIENCIAS DA SAUDE::MEDICINA |
dc.subject.eng.fl_str_mv |
Hypermethioninemia Methionine Oxidative Stress Zebrafish Transgenerational |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::MEDICINA |
description |
Methionine participates directly or indirectly in the formation of other amino acids, neurotransmitters and in methylation processes, ensuring the homeostasis of an organism. However, genetic causes, called innate metabolism errors, or non-genetic causes can increase plasma methionine levels, a condition known as hypermethioninemia. Consequently, myopathies, liver disease and neurological problems can arise, and even a transient increase can cause toxicological effects. In addition, given the role of methionine in epigenetic control processes, subsequent generation may also be affected. However, assessments of the effects of transient hypermethioninemia are scarce and the mechanisms underlying this pathology have not yet been explored. Thus, the aim of this study was to explore the effects of transient hypermethioninemia in zebrafish parents and their offspring. Morphological changes, heartbeat, survival and locomotion were evaluated in the offspring in the larval stage, while anxiety, aggression, social interaction and aversive memory were evaluated in the parents and in the offspring in the adult stage. The levels of neurotransmitters and amino acids and the oxidative profile have also been explored in parents exposed to methionine and their offspring. The results obtained demonstrate that an exposure to methionine has long-lasting neurotoxic effects, since after the removal of methionine the exposed animals showed a decrease in anxiety, a decrease in aggression, and memory deficits. Concomitant to this, the levels of carnitine, creatine, cysteine and epinephrine were altered and redox homeostasis impaired seen by decreased levels of catalase, superoxide dismutase and total thiol content. We also observed that a transient increase in methionine has transgenerational effects, since the offspring of the exposed parents was hyperactive in the larval stage and, in the adult stage, also showed a decrease in anxiety with increased levels of neurotransmitters and an altered oxidative profile with increase of DCF levels. Therefore, high levels of methionine, even if transient, can cause long-lasting behavioral and neurochemical changes with effects also observed in the subsequent generation. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-11-20T17:34:50Z |
dc.date.issued.fl_str_mv |
2020-03-23 |
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http://tede2.pucrs.br/tede2/handle/tede/9418 |
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http://tede2.pucrs.br/tede2/handle/tede/9418 |
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por |
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-721401722658532398 |
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500 500 500 600 |
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-224747486637135387 |
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-969369452308786627 |
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Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
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Programa de P?s-Gradua??o em Medicina e Ci?ncias da Sa?de |
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PUCRS |
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Brasil |
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Escola de Medicina |
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Pontif?cia Universidade Cat?lica do Rio Grande do Sul |
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