Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta
Ano de defesa: | 2019 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Não Informado pela instituição
|
Departamento: |
Não Informado pela instituição
|
País: |
Não Informado pela instituição
|
Palavras-chave em Português: | |
Link de acesso: | 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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Estresse 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 offspringBDNFEixo HPAEstresse oxidativoMorfinaHPA axisOxidative stressMorphineCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAccording 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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESSegundo 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.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasBurger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Pase, Camila SimonettiPavanato, Maria AmáliaCarpes, Pâmela Billig MelloOliveira, Sara Marchesan deVey, Luciana Taschetto2021-08-17T18:53:39Z2021-08-17T18:53:39Z2019-10-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/21979porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-08-18T06:03:12Zoai:repositorio.ufsm.br:1/21979Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-08-18T06:03:12Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Estresse pré e pós natal afetam aspectos morfológicos, bioquímicos e moleculares do eixo cortico-hipotalâmico na prole adulta 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.none.fl_str_mv |
Burger, Marilise Escobar http://lattes.cnpq.br/9128090974948413 Pase, Camila Simonetti Pavanato, Maria Amália Carpes, Pâmela Billig Mello Oliveira, Sara Marchesan de |
dc.contributor.author.fl_str_mv |
Vey, Luciana Taschetto |
dc.subject.por.fl_str_mv |
BDNF Eixo HPA Estresse oxidativo Morfina HPA axis Oxidative stress Morphine CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
BDNF Eixo HPA Estresse oxidativo Morfina HPA axis Oxidative stress Morphine 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.none.fl_str_mv |
2019-10-18 2021-08-17T18:53:39Z 2021-08-17T18:53:39Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/21979 |
url |
http://repositorio.ufsm.br/handle/1/21979 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805930085584207872 |