Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus

Detalhes bibliográficos
Autor(a) principal: Lima, Taís de Campos
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFU
Texto Completo: https://repositorio.ufu.br/handle/123456789/12394
https://doi.org/10.14393/ufu.di.2013.193
Resumo: Glycemic control during gestational period may be challenging for both diabetic and non-diabetic patients, who may develop gestational diabetes. A series of studies has been indicating that infants of diabetic mothers have also chronic changes that predispose them to diseases throughout life. Although there is no description of alterations in the development of peripheral sensory system, a study in rats by Germani et al. (1999) showed that the levels of mRNA for the neurotrophic factors NGF and BDNF are greatly reduced in the offspring of rats in which diabetes. Since these growth factors are essentials for the development of nociceptive neurons, the present study aims to evaluate if the exposure of rats in utero to maternal diabetes induced by alloxan alters the development of nociceptive peripheral system. The evaluation in newborn animals was done on primary cultures of dorsal root ganglia. Histological evaluation of primary sensory neurons in adult animals was performed using frozen sections of the dorsal root ganglia (L5). To assess the types of sensory fibers it was performed a morphometric analysis in order to categorize neurons according to soma diameters. Neurons were separated in small (<30 microns), medium (between 30 and 40 mm) and large soma (> 40 mm). There was no difference in the distribution of neurons by size in newborns or adults. The subtypes of neurons were also categorized according to the fluorescent labeling: TRPV1 (vanilloid receptor present only on nociceptors), NFH (H neurofilament present in large diameter fibers), substance P (present in peptidergic nociceptive neurons) and IB4 (non peptidergic nociceptive neurons). In the cultures of newborn rats, no difference was observed between the proportions of neurons that were marked positive for the selected molecules. Adult offspring of diabetic rats had a lower proportion of large neurons positive for NFH (P = 0.0078) and a higher proportion of positive neurons for substance P and isolectin B4 (P = 0.0291 and P = 0.0353, respectively). We also performed behavioral tests that showed a lower mechanical sensitivity (electronic Von Frey) of animals in offspring of diabetic mothers after 6 hours of intrapantar carrageenan injection. The offspring of diabetic rats showed an enhanced thermal sensitivity. In the formalin test, it was observed an increased response in the beginning of the second phase, which corresponds to the inflammatory phase of this test. Therefore, in this study it was found that nociceptive responses are altered in adult offspring of diabetic rats and these changes are accompanied by changes in the profile of neurons present in the dorsal root ganglion.
id UFU_5b855fe9f3d6e6862e67ccd39dd5472f
oai_identifier_str oai:repositorio.ufu.br:123456789/12394
network_acronym_str UFU
network_name_str Repositório Institucional da UFU
repository_id_str
spelling Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitusMorphological and functional evaluation of the nociceptive sensory system in the offspring of rats with diabetes mellitusDiabetesGestaçãoDorGânglio da raiz dorsalDiabetesGestationPainDorsal root gangliaCNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULARGlycemic control during gestational period may be challenging for both diabetic and non-diabetic patients, who may develop gestational diabetes. A series of studies has been indicating that infants of diabetic mothers have also chronic changes that predispose them to diseases throughout life. Although there is no description of alterations in the development of peripheral sensory system, a study in rats by Germani et al. (1999) showed that the levels of mRNA for the neurotrophic factors NGF and BDNF are greatly reduced in the offspring of rats in which diabetes. Since these growth factors are essentials for the development of nociceptive neurons, the present study aims to evaluate if the exposure of rats in utero to maternal diabetes induced by alloxan alters the development of nociceptive peripheral system. The evaluation in newborn animals was done on primary cultures of dorsal root ganglia. Histological evaluation of primary sensory neurons in adult animals was performed using frozen sections of the dorsal root ganglia (L5). To assess the types of sensory fibers it was performed a morphometric analysis in order to categorize neurons according to soma diameters. Neurons were separated in small (<30 microns), medium (between 30 and 40 mm) and large soma (> 40 mm). There was no difference in the distribution of neurons by size in newborns or adults. The subtypes of neurons were also categorized according to the fluorescent labeling: TRPV1 (vanilloid receptor present only on nociceptors), NFH (H neurofilament present in large diameter fibers), substance P (present in peptidergic nociceptive neurons) and IB4 (non peptidergic nociceptive neurons). In the cultures of newborn rats, no difference was observed between the proportions of neurons that were marked positive for the selected molecules. Adult offspring of diabetic rats had a lower proportion of large neurons positive for NFH (P = 0.0078) and a higher proportion of positive neurons for substance P and isolectin B4 (P = 0.0291 and P = 0.0353, respectively). We also performed behavioral tests that showed a lower mechanical sensitivity (electronic Von Frey) of animals in offspring of diabetic mothers after 6 hours of intrapantar carrageenan injection. The offspring of diabetic rats showed an enhanced thermal sensitivity. In the formalin test, it was observed an increased response in the beginning of the second phase, which corresponds to the inflammatory phase of this test. Therefore, in this study it was found that nociceptive responses are altered in adult offspring of diabetic rats and these changes are accompanied by changes in the profile of neurons present in the dorsal root ganglion.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorMestre em Biologia Celular e Estrutural AplicadasO período de gestação representa um desafio para o controle glicêmico tanto de indivíduos diabéticos quanto de não diabéticos, que podem desenvolver o diabetes gestacional neste período. Além das complicações médicas que se evidenciam ao nascimento dos indivíduos filhos de mães diabéticas, uma série de estudos, em humanos e animais, vem indicando que estes indivíduos possuem também alterações crônicas que os predispõe a apresentarem patologias ao longo da vida. Embora não exista descrição de alterações no desenvolvimento do sistema nervoso periférico, um estudo realizado em ratos por Germani et al. (1999) mostrou que os níveis de RNAm para os fatores neurotróficos NGF e BDNF estão bastante reduzidos na prole de ratas diabéticas. Visto que estes fatores de crescimento são essenciais para o desenvolvimento do sistema sensorial periférico, o estudo tem como objetivo avaliar se a exposição do rato in útero ao diabetes materno induzido por aloxana altera o desenvolvimento do sistema sensorial nociceptivo periférico. A avaliação nos animais recém-nascidos foi feita em culturas primárias de gânglios da raiz dorsal. A avaliação histológica de neurônios sensoriais primários de animais adultos foi realizada através de cortes congelados dos gânglios (L5). Para avaliar se existia alteração nos tipos de fibras sensoriais foi realizada uma análise morfométrica entre neurônios de pequeno (<30 μm), médio (entre 30 e 40 μm) e grande diâmetro (>40 μm). Não foi detectada diferença no padrão de distribuição dos neurônios nos testes realizados em animais neonatos e adultos. Os subtipos de neurônios foram ainda categorizados de acordo com a marcação fluorescente: TRPV1(receptor vanilóide presente apenas em nociceptores), NFH (neurofilamento H presente em fibras de diâmetro grande), substância P (presente em neurônios nociceptivos peptidérgicos) e IB4 (nociceptivos não peptidérgicos). Nas culturas de ratos recém-nascidos, não foi observada diferença entre as proporções de neurônios que apresentaram marcação positiva para os diferentes marcadores testados. Os animais filhos de ratas diabéticas apresentaram uma menor proporção de neurônios grandes positivos para NFH (P=0.0078) e uma maior proporção de neurônios com marcação para substância P e isolectina B4 (P=0.0291 e P=0.0353, respectivamente). Foram realizados também testes comportamentais que revelaram uma menor sensibilidade mecânica dos animais filhos de mães diabéticas no teste de Von Frey eletrônico após 6 horas da injeção de carragenina. Os animais filhos de ratas diabéticas apresentarem uma maior sensibilidade térmica em condições basais. No teste da formalina, foi observado que os animais tratados apresentam um aumento de resposta no início da segunda fase, que seria a fase inflamatória deste teste. Portanto, neste estudo foi verificado que as respostas nociceptivas estão alteradas em animais adultos filhos de ratas diabéticas e que estas alterações são acompanhadas por mudanças no perfil dos neurônios presentes no gânglio da raiz dorsal.Universidade Federal de UberlândiaBRPrograma de Pós-graduação em Biologia Celular e Estrutural AplicadasCiências BiomédicasUFULotufo, Celina Monteiro da Cruzhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794313Y5Rodrigues, Aldo Rogelis Aquileshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794651T3Balbi, Ana Paula Coelhohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4778490T4Lima, Taís de Campos2016-06-22T18:31:49Z2013-10-112016-06-22T18:31:49Z2013-03-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfLIMA, Taís de Campos. Morphological and functional evaluation of the nociceptive sensory system in the offspring of rats with diabetes mellitus. 2013. 63 f. Dissertação (Mestrado em Ciências Biomédicas) - Universidade Federal de Uberlândia, Uberlândia, 2013. DOI https://doi.org/10.14393/ufu.di.2013.193https://repositorio.ufu.br/handle/123456789/12394https://doi.org/10.14393/ufu.di.2013.193porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2022-09-08T18:20:28Zoai:repositorio.ufu.br:123456789/12394Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2022-09-08T18:20:28Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false
dc.title.none.fl_str_mv Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus
Morphological and functional evaluation of the nociceptive sensory system in the offspring of rats with diabetes mellitus
title Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus
spellingShingle Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus
Lima, Taís de Campos
Diabetes
Gestação
Dor
Gânglio da raiz dorsal
Diabetes
Gestation
Pain
Dorsal root ganglia
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAR
title_short Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus
title_full Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus
title_fullStr Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus
title_full_unstemmed Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus
title_sort Avaliação morfológica e funcional do sistema sensorial nociceptivo na prole de ratas com diabetes mellitus
author Lima, Taís de Campos
author_facet Lima, Taís de Campos
author_role author
dc.contributor.none.fl_str_mv Lotufo, Celina Monteiro da Cruz
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794313Y5
Rodrigues, Aldo Rogelis Aquiles
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794651T3
Balbi, Ana Paula Coelho
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4778490T4
dc.contributor.author.fl_str_mv Lima, Taís de Campos
dc.subject.por.fl_str_mv Diabetes
Gestação
Dor
Gânglio da raiz dorsal
Diabetes
Gestation
Pain
Dorsal root ganglia
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAR
topic Diabetes
Gestação
Dor
Gânglio da raiz dorsal
Diabetes
Gestation
Pain
Dorsal root ganglia
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAR
description Glycemic control during gestational period may be challenging for both diabetic and non-diabetic patients, who may develop gestational diabetes. A series of studies has been indicating that infants of diabetic mothers have also chronic changes that predispose them to diseases throughout life. Although there is no description of alterations in the development of peripheral sensory system, a study in rats by Germani et al. (1999) showed that the levels of mRNA for the neurotrophic factors NGF and BDNF are greatly reduced in the offspring of rats in which diabetes. Since these growth factors are essentials for the development of nociceptive neurons, the present study aims to evaluate if the exposure of rats in utero to maternal diabetes induced by alloxan alters the development of nociceptive peripheral system. The evaluation in newborn animals was done on primary cultures of dorsal root ganglia. Histological evaluation of primary sensory neurons in adult animals was performed using frozen sections of the dorsal root ganglia (L5). To assess the types of sensory fibers it was performed a morphometric analysis in order to categorize neurons according to soma diameters. Neurons were separated in small (<30 microns), medium (between 30 and 40 mm) and large soma (> 40 mm). There was no difference in the distribution of neurons by size in newborns or adults. The subtypes of neurons were also categorized according to the fluorescent labeling: TRPV1 (vanilloid receptor present only on nociceptors), NFH (H neurofilament present in large diameter fibers), substance P (present in peptidergic nociceptive neurons) and IB4 (non peptidergic nociceptive neurons). In the cultures of newborn rats, no difference was observed between the proportions of neurons that were marked positive for the selected molecules. Adult offspring of diabetic rats had a lower proportion of large neurons positive for NFH (P = 0.0078) and a higher proportion of positive neurons for substance P and isolectin B4 (P = 0.0291 and P = 0.0353, respectively). We also performed behavioral tests that showed a lower mechanical sensitivity (electronic Von Frey) of animals in offspring of diabetic mothers after 6 hours of intrapantar carrageenan injection. The offspring of diabetic rats showed an enhanced thermal sensitivity. In the formalin test, it was observed an increased response in the beginning of the second phase, which corresponds to the inflammatory phase of this test. Therefore, in this study it was found that nociceptive responses are altered in adult offspring of diabetic rats and these changes are accompanied by changes in the profile of neurons present in the dorsal root ganglion.
publishDate 2013
dc.date.none.fl_str_mv 2013-10-11
2013-03-18
2016-06-22T18:31:49Z
2016-06-22T18:31:49Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv LIMA, Taís de Campos. Morphological and functional evaluation of the nociceptive sensory system in the offspring of rats with diabetes mellitus. 2013. 63 f. Dissertação (Mestrado em Ciências Biomédicas) - Universidade Federal de Uberlândia, Uberlândia, 2013. DOI https://doi.org/10.14393/ufu.di.2013.193
https://repositorio.ufu.br/handle/123456789/12394
https://doi.org/10.14393/ufu.di.2013.193
identifier_str_mv LIMA, Taís de Campos. Morphological and functional evaluation of the nociceptive sensory system in the offspring of rats with diabetes mellitus. 2013. 63 f. Dissertação (Mestrado em Ciências Biomédicas) - Universidade Federal de Uberlândia, Uberlândia, 2013. DOI https://doi.org/10.14393/ufu.di.2013.193
url https://repositorio.ufu.br/handle/123456789/12394
https://doi.org/10.14393/ufu.di.2013.193
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Uberlândia
BR
Programa de Pós-graduação em Biologia Celular e Estrutural Aplicadas
Ciências Biomédicas
UFU
publisher.none.fl_str_mv Universidade Federal de Uberlândia
BR
Programa de Pós-graduação em Biologia Celular e Estrutural Aplicadas
Ciências Biomédicas
UFU
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFU
instname:Universidade Federal de Uberlândia (UFU)
instacron:UFU
instname_str Universidade Federal de Uberlândia (UFU)
instacron_str UFU
institution UFU
reponame_str Repositório Institucional da UFU
collection Repositório Institucional da UFU
repository.name.fl_str_mv Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)
repository.mail.fl_str_mv diinf@dirbi.ufu.br
_version_ 1813711493412159488