Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta

Detalhes bibliográficos
Autor(a) principal: Vey, Luciana Taschetto
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional Manancial UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/21979
Resumo: According to the World Health Organization (2010), stress is recognized and identified as the evil of the century due to its chronicity and repercussions that are directly connected to life quality, family and society. Pre-natal animal models of stress and neonatal isolation reproduce many characteristics of chronic stress or adverse experiences lived in the beginning of life. Therefore, this study aimed to investigate if stress during the fetal and neonatal period could modify biochemical, morphologic and molecular parameters in adult offspring. In the first experiment (EXP1), pregnant Wistar rats were subjected to prenatal stress for two weeks while the pregnant rats in the second experiment (EXP 2) were not handled until their pups‟ birth, which were exposed to a neonatal isolation protocol. Biochemical, morphological and molecular analyzes were performed on postnatal day 50 of both experiments. In EXP1, animals exposed to maternal stress showed increased oxidative stress, persistent histological changes, as well as neurotrophin changes related to cell plasticity. Inversely, animals exposed to neonatal management (EXP2) showed better memory performance, which was accompanied by increased neurogenesis observed by increased neurotrophins involved in neuroplasticity, as well as in histological analysis. Considering the strong emotional stress involvement with increased corticosterone levels, we also decided to investigate some molecular markers related to HPA axis stimulation through glucocorticoid receptor dosage whose immunoreactivity was reduced in the EXP1 group at the same time that increased in the EXP2. As stress exposure has been related to drug addiction, in both experimental protocols a group of animals was exposed to morphine with consequent evaluation of mu opioid receptor density. As a result, EXP1 animals showed increased of mu opioid receptor immunoreactivity after morphine exposure while animals from EXP2 showed increased immunoreactivity, which was also observed in animals not exposed to morphine, indicating a change per se due to postnatal handling. The results presented indicate that stressful experiences during the prenatal period may develop persistent deleterious changes throughout life. On the other hand, neuroadaptive changes resulting from neonatal isolation showed an ability to overcome stress showing an increase in persistence resilience during their development until adulthood.
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spelling 2021-08-17T18:53:39Z2021-08-17T18:53:39Z2019-10-18http://repositorio.ufsm.br/handle/1/21979According to the World Health Organization (2010), stress is recognized and identified as the evil of the century due to its chronicity and repercussions that are directly connected to life quality, family and society. Pre-natal animal models of stress and neonatal isolation reproduce many characteristics of chronic stress or adverse experiences lived in the beginning of life. Therefore, this study aimed to investigate if stress during the fetal and neonatal period could modify biochemical, morphologic and molecular parameters in adult offspring. In the first experiment (EXP1), pregnant Wistar rats were subjected to prenatal stress for two weeks while the pregnant rats in the second experiment (EXP 2) were not handled until their pups‟ birth, which were exposed to a neonatal isolation protocol. Biochemical, morphological and molecular analyzes were performed on postnatal day 50 of both experiments. In EXP1, animals exposed to maternal stress showed increased oxidative stress, persistent histological changes, as well as neurotrophin changes related to cell plasticity. Inversely, animals exposed to neonatal management (EXP2) showed better memory performance, which was accompanied by increased neurogenesis observed by increased neurotrophins involved in neuroplasticity, as well as in histological analysis. Considering the strong emotional stress involvement with increased corticosterone levels, we also decided to investigate some molecular markers related to HPA axis stimulation through glucocorticoid receptor dosage whose immunoreactivity was reduced in the EXP1 group at the same time that increased in the EXP2. As stress exposure has been related to drug addiction, in both experimental protocols a group of animals was exposed to morphine with consequent evaluation of mu opioid receptor density. As a result, EXP1 animals showed increased of mu opioid receptor immunoreactivity after morphine exposure while animals from EXP2 showed increased immunoreactivity, which was also observed in animals not exposed to morphine, indicating a change per se due to postnatal handling. The results presented indicate that stressful experiences during the prenatal period may develop persistent deleterious changes throughout life. On the other hand, neuroadaptive changes resulting from neonatal isolation showed an ability to overcome stress showing an increase in persistence resilience during their development until adulthood.Segundo a Organização Mundial da Saúde (2010), o estresse é reconhecido por sua cronicidade e identificado como o mal do século XXI, cujas repercussões estão diretamente ligadas à qualidade de vida do indivíduo, da família e da sociedade. Modelos animal de estresse pré-natal e isolamento neonatal reproduzem muitas características do estresse crônico ou experiências adversas sofridas no início da vida. Assim, o presente estudo objetivou investigar se o estresse durante os períodos fetal e neonatal poderia modificar parâmetros bioquímicos, morfológicos e moleculares na prole adulta. No primeiro experimento (EXP1), ratas Wistar prenhes foram submetidas ao estresse pré-natal durante duas semanas, enquanto no segundo (EXP 2), as ratas prenhes não foram manuseadas até o nascimento dos filhotes, os quais foram expostos a um protocolo de isolamento neonatal. As análises bioquímicas, morfológicas e moleculares foram realizadas no dia pós-natal 50 de ambos os experimentos. No EXP1, os animais expostos ao estresse materno apresentaram aumento de estresse oxidativo, modificações histológicas persistentes, bem como alterações de neurotrofinas relacionadas à plasticidade celular. Inversamente, animais expostos ao manuseio neonatal (EXP2), apresentaram melhor desempenho de memória, a qual foi acompanhada do aumento da neurogênese observada pelo aumento das neurotrofinas envolvidas na neuroplasticidade, como também na análise histológica. Considerando o forte envolvimento do estresse emocional com níveis aumentados de corticosterona, decidimos investigar também alguns marcadores moleculares relacionados ao estímulo do eixo hipotálamo-pituitária- adrenal através da dosagem dos receptores de glicocorticoides, cuja imunoreatividade foi reduzida no grupo de animais do EXP1 e aumentada nos animais do EXP2. Como a exposição ao estresse tem sido relacionada ao desenvolvimento de drogadição, em ambos os protocolos experimentais um grupo de animais foi exposto à morfina com consequente avaliação da densidade dos receptores mu opioides. Como resultado, animais do EXP1 apresentaram imunoreatividade aumentada deste receptor após exposição à morfina, enquanto os animais provenientes do EXP2 mostraram tal imunoreatividade aumentada, a qual foi também observada nos animais não expostos à morfina, indicando uma modificação per se do manuseio pós-natal. Os resultados aqui apresentados indicam que experiências estressantes durante o período pré-natal podem desenvolver alterações deletérias persistentes ao longo da vida. Por outro lado, as modificações neuroadaptativas consequentes ao isolamento neonatal mostraram capacidade para superar o estresse, caracterizando um aumento de resiliência persistente durante o desenvolvimento rumo à vida adulta.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessBDNFEixo HPAEstresse oxidativoMorfinaHPA axisOxidative stressMorphineCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEstresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adultaPre and postnatal stress affect morphological, biochemical and molecular aspects of cortico-hypothalamic axis in adult offspringinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBurger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Pase, Camila SimonettiPavanato, Maria AmáliaCarpes, Pâmela Billig MelloOliveira, Sara Marchesan dehttp://lattes.cnpq.br/2603708899899969Vey, Luciana Taschetto200800000002600600600600600600600cea6b067-f9a7-4654-8ec5-65f1c465c1a830fed64a-1648-405f-87f8-61d6f65e47dc174344e7-e6bd-4a37-ae4d-25fc5d9d64b2f9c09a50-0698-4450-9e10-ac44830c8837a9ec91bc-8746-4287-9021-591571ad4d804075277b-8b36-46ac-b25d-abf48b5aa548reponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCBBT_2019_VEY_LUCIANA.pdfTES_PPGCBBT_2019_VEY_LUCIANA.pdfTeseapplication/pdf2409270http://repositorio.ufsm.br/bitstream/1/21979/1/TES_PPGCBBT_2019_VEY_LUCIANA.pdfa92881d7ee8f9243cd644eb284a1d348MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
dc.title.alternative.eng.fl_str_mv Pre and postnatal stress affect morphological, biochemical and molecular aspects of cortico-hypothalamic axis in adult offspring
title Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
spellingShingle Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
Vey, Luciana Taschetto
BDNF
Eixo HPA
Estresse oxidativo
Morfina
HPA axis
Oxidative stress
Morphine
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
title_full Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
title_fullStr Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
title_full_unstemmed Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
title_sort Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
author Vey, Luciana Taschetto
author_facet Vey, Luciana Taschetto
author_role author
dc.contributor.advisor1.fl_str_mv Burger, Marilise Escobar
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9128090974948413
dc.contributor.referee1.fl_str_mv Pase, Camila Simonetti
dc.contributor.referee2.fl_str_mv Pavanato, Maria Amália
dc.contributor.referee3.fl_str_mv Carpes, Pâmela Billig Mello
dc.contributor.referee4.fl_str_mv Oliveira, Sara Marchesan de
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/2603708899899969
dc.contributor.author.fl_str_mv Vey, Luciana Taschetto
contributor_str_mv Burger, Marilise Escobar
Pase, Camila Simonetti
Pavanato, Maria Amália
Carpes, Pâmela Billig Mello
Oliveira, Sara Marchesan de
dc.subject.por.fl_str_mv BDNF
Eixo HPA
Estresse oxidativo
Morfina
topic BDNF
Eixo HPA
Estresse oxidativo
Morfina
HPA axis
Oxidative stress
Morphine
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
dc.subject.eng.fl_str_mv HPA axis
Oxidative stress
Morphine
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description According to the World Health Organization (2010), stress is recognized and identified as the evil of the century due to its chronicity and repercussions that are directly connected to life quality, family and society. Pre-natal animal models of stress and neonatal isolation reproduce many characteristics of chronic stress or adverse experiences lived in the beginning of life. Therefore, this study aimed to investigate if stress during the fetal and neonatal period could modify biochemical, morphologic and molecular parameters in adult offspring. In the first experiment (EXP1), pregnant Wistar rats were subjected to prenatal stress for two weeks while the pregnant rats in the second experiment (EXP 2) were not handled until their pups‟ birth, which were exposed to a neonatal isolation protocol. Biochemical, morphological and molecular analyzes were performed on postnatal day 50 of both experiments. In EXP1, animals exposed to maternal stress showed increased oxidative stress, persistent histological changes, as well as neurotrophin changes related to cell plasticity. Inversely, animals exposed to neonatal management (EXP2) showed better memory performance, which was accompanied by increased neurogenesis observed by increased neurotrophins involved in neuroplasticity, as well as in histological analysis. Considering the strong emotional stress involvement with increased corticosterone levels, we also decided to investigate some molecular markers related to HPA axis stimulation through glucocorticoid receptor dosage whose immunoreactivity was reduced in the EXP1 group at the same time that increased in the EXP2. As stress exposure has been related to drug addiction, in both experimental protocols a group of animals was exposed to morphine with consequent evaluation of mu opioid receptor density. As a result, EXP1 animals showed increased of mu opioid receptor immunoreactivity after morphine exposure while animals from EXP2 showed increased immunoreactivity, which was also observed in animals not exposed to morphine, indicating a change per se due to postnatal handling. The results presented indicate that stressful experiences during the prenatal period may develop persistent deleterious changes throughout life. On the other hand, neuroadaptive changes resulting from neonatal isolation showed an ability to overcome stress showing an increase in persistence resilience during their development until adulthood.
publishDate 2019
dc.date.issued.fl_str_mv 2019-10-18
dc.date.accessioned.fl_str_mv 2021-08-17T18:53:39Z
dc.date.available.fl_str_mv 2021-08-17T18:53:39Z
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Centro de Ciências Naturais e Exatas
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dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Bioquímica
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas
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