Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal

Detalhes bibliográficos
Ano de defesa: 2017
Autor(a) principal: Pimentel, Luciana Cristina lattes
Orientador(a): Cysneiros, Roberta Monterazzo lattes
Banca de defesa: Carreiro, Luiz Renato Rodrigues lattes, Silva, Regina Cláudia Barbosa da lattes, Ribeiro, Miriam Oliveira lattes, Scorza, Fulvio Alexandre lattes
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Presbiteriana Mackenzie
Programa de Pós-Graduação: Distúrbios do Desenvolvimento
Departamento: Centro de Ciências Biológicas e da Saúde (CCBS)
País: Brasil
Palavras-chave em Português:
Área do conhecimento CNPq:
Link de acesso: http://dspace.mackenzie.br/handle/10899/24549
Resumo: The pilocarpine model of Temporal Lobe Epilepsy (TLE) reliably reproduces the characteristics found in TLE in humans and provokes Attention-deficit/hyperactivity disorder (ADHD)-like behaviors in rodents. However, it is not known if these behavioral changes are associated with variations on genetic expression. The present study aimed to investigate behavior patterns and molecular indicators of ADHD in the pilocarpine model of TLE. Male Wistar rats at 25 day of age were submitted to animal model of TLE by pilocarpine injection (350 mg/kg, ip) and a control group received saline 0.9%. The behavioural tests (open field and operant conditioning box) started from 28 days postnatal. Through Real-Time Polimerase Chain Reaction (RT-PCR), were evaluated the expression of somatostatin, mGluR7 and dopaminergic receptors subtype D1 and subtype D5, in the pre-frontal cortex and hippocampus. Behavioral parameters were analysed using Mixed ANOVA, followed by Bonferroni for post-hoc testing. For data analyses of gene expression, t-Student test was used. The data were expressed as mean ± standard error and p-values of 0.05 or less were considered significant. The analyses were effectuated using commercial program (Prism 5.03 for windows). Results in open field for total locomotion revealed a significant difference between groups (F[1,144]=9,32 p=0,0076) and between sessions (F[9,144]= 5,74 p<0,0001), nor effect of interaction between factors (F[9,144]=9,32 NS); and for central locomotion, in percentage, was a significantly diferente between groups (F[1,144]=5,54 p=0,031), effect of interaction between the factors (F[9,144]=3,41 p=0,0008), with no difference between sessions (F[9,144]=0,75 NS). In Skinner box, no significant differences were found between the groups in experimental conditions of this study. For RT-PCR there were observed no significant differences in the expression relative of mRNA in the analyzed genes. We concluded that animals with TLE exhibited elevated locomotor activity and reduced level of anxiety-related behavior. There was observed no deficit of attention and impulsive-like behavior. There were found no variations for somatostatin gene expression, mGluR7 and dopaminergic receptors D1 and D5, in prefrontal cortex and in hippocampus. Behavioral alterations observed in the model of TLE probably are not related to gene alterations of somatostatin and these receptors.
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spelling 2017-04-03T13:31:25Z2020-05-28T18:09:22Z2020-05-28T18:09:22Z2017-02-09PIMENTEL, Luciana Cristina. Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal. 2017. 89 f. Tese( Distúrbios do Desenvolvimento) - Universidade Presbiteriana Mackenzie, São Paulo.http://dspace.mackenzie.br/handle/10899/24549The pilocarpine model of Temporal Lobe Epilepsy (TLE) reliably reproduces the characteristics found in TLE in humans and provokes Attention-deficit/hyperactivity disorder (ADHD)-like behaviors in rodents. However, it is not known if these behavioral changes are associated with variations on genetic expression. The present study aimed to investigate behavior patterns and molecular indicators of ADHD in the pilocarpine model of TLE. Male Wistar rats at 25 day of age were submitted to animal model of TLE by pilocarpine injection (350 mg/kg, ip) and a control group received saline 0.9%. The behavioural tests (open field and operant conditioning box) started from 28 days postnatal. Through Real-Time Polimerase Chain Reaction (RT-PCR), were evaluated the expression of somatostatin, mGluR7 and dopaminergic receptors subtype D1 and subtype D5, in the pre-frontal cortex and hippocampus. Behavioral parameters were analysed using Mixed ANOVA, followed by Bonferroni for post-hoc testing. For data analyses of gene expression, t-Student test was used. The data were expressed as mean ± standard error and p-values of 0.05 or less were considered significant. The analyses were effectuated using commercial program (Prism 5.03 for windows). Results in open field for total locomotion revealed a significant difference between groups (F[1,144]=9,32 p=0,0076) and between sessions (F[9,144]= 5,74 p<0,0001), nor effect of interaction between factors (F[9,144]=9,32 NS); and for central locomotion, in percentage, was a significantly diferente between groups (F[1,144]=5,54 p=0,031), effect of interaction between the factors (F[9,144]=3,41 p=0,0008), with no difference between sessions (F[9,144]=0,75 NS). In Skinner box, no significant differences were found between the groups in experimental conditions of this study. For RT-PCR there were observed no significant differences in the expression relative of mRNA in the analyzed genes. We concluded that animals with TLE exhibited elevated locomotor activity and reduced level of anxiety-related behavior. There was observed no deficit of attention and impulsive-like behavior. There were found no variations for somatostatin gene expression, mGluR7 and dopaminergic receptors D1 and D5, in prefrontal cortex and in hippocampus. Behavioral alterations observed in the model of TLE probably are not related to gene alterations of somatostatin and these receptors.O modelo de Epilepsia do Lobo Temporal (ELT), pela administração sistêmica de pilocarpina, reproduz de forma fidedigna as características encontradas na ELT em humanos e provoca alterações comportamentais em ratos semelhantes aos sintomas do Transtorno de Déficit de Atenção e Hiperatividade (TDAH). Entretanto, não se sabe se essas alterações comportamentais estão associadas a variações na expressão gênica. O objetivo desse estudo foi descrever padrões comportamentais e indicadores moleculares do TDAH no modelo de ELT induzido por pilocarpina. Ratos Wistar machos com 25 dias pós-natal foram submetidos ao modelo de epilepsia pela administração de pilocarpina (350 mg/kg, ip) e os controles receberam salina. Os testes comportamentais (campo aberto e caixa de condicionamento operante) começaram a partir de 28 dias pós-natal. Através da Reação em Cadeia de Polimerase em Tempo Real (PCR-RT), avaliou-se a expressão de somatostatina, mGluR7 e dos receptores dopaminérgicos subtipo D1 e subtipo D5, no córtex pré-frontal e no hipocampo. Os parâmetros comportamentais foram analisados empregando-se a ANOVA Mista, seguido pelo pós-teste de Bonferroni. Para a análise de dados da expressão gênica, empregou-se teste t-Student. Os resultados foram expressos com média ± erro padrão. As diferenças foram consideradas significantes para um valor de p < 0,05. As análises foram efetuadas utilizando-se o Prism versão comercial 5.03 para Windows. Os resultados no campo aberto demonstraram diferenças estatisticamente significantes para a locomoção total, entre os grupos (F[1,144]=9,32 p=0,0076) e entre as sessões (F[9,144]= 5,74 p<0,0001), sem efeito da interação entre os fatores (F[9,144]=9,32 NS); e para atividade locomotora na zona central, em percetagem, diferença significante entre os grupos (F[1,144]=5,54 p=0,031), com efeito da interação entre os fatores (F[9,144]=3,41 p=0,0008), sem diferença entre as sessões (F[9,144]=0,75 NS). Na caixa de condicionamento operante, não foram encontradas diferenças significativas entre os grupos nas condições experimentais desse estudo. Para a PCR-RT não foram observadas diferenças significantes na expressão relativa de RNAm dos genes analisados. Em conclusão, os animais com ELT apresentaram aumento da atividade locomotora e redução do comportamento tipo-ansioso. Não foram observados déficit de atenção e comportamento tipoimpulsivo. Não foram encontradas variações para a expressão gênica de somatostatina, mGluR7 e dos receptores dopaminérgicos D1 e D5, no CPF e no hipocampo. As alterações comportamentais observadas no modelo de ELT provavelmente não estão relacionadas a alterações gênicas da somatostatina e desses receptores.application/pdfporUniversidade Presbiteriana MackenzieDistúrbios do DesenvolvimentoUPMBrasilCentro de Ciências Biológicas e da Saúde (CCBS)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesspilocarpinaTDAHepilepsiareceptor dopaminérgicoCNPQ::CIENCIAS DA SAUDE::FARMACIAAvaliação comportamental e molecular em um modelo de epilepsia do lobo temporalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisCysneiros, Roberta Monterazzohttp://lattes.cnpq.br/9822955080635086Carreiro, Luiz Renato Rodrigueshttp://lattes.cnpq.br/0203967709311323Silva, Regina Cláudia Barbosa dahttp://lattes.cnpq.br/7507421915981968Ribeiro, Miriam Oliveirahttp://lattes.cnpq.br/7069953370349465Scorza, Fulvio Alexandrehttp://lattes.cnpq.br/3665794780601169http://lattes.cnpq.br/8835810156810156Pimentel, Luciana Cristinahttp://tede.mackenzie.br/jspui/retrieve/13842/Luciana%20Cristina%20Pimentel.pdf.jpghttp://tede.mackenzie.br/jspui/bitstream/tede/3178/5/Luciana%20Cristina%20Pimentel.pdfpilocarpineADHDepilepsydopaminergic receptorreponame:Biblioteca Digital de Teses e Dissertações do Mackenzieinstname:Universidade Presbiteriana Mackenzie (MACKENZIE)instacron:MACKENZIE10899/245492020-05-28 15:09:22.205Biblioteca Digital de Teses e Dissertaçõeshttp://tede.mackenzie.br/jspui/PRI
dc.title.por.fl_str_mv Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal
title Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal
spellingShingle Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal
Pimentel, Luciana Cristina
pilocarpina
TDAH
epilepsia
receptor dopaminérgico
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal
title_full Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal
title_fullStr Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal
title_full_unstemmed Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal
title_sort Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal
author Pimentel, Luciana Cristina
author_facet Pimentel, Luciana Cristina
author_role author
dc.contributor.advisor1.fl_str_mv Cysneiros, Roberta Monterazzo
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/9822955080635086
dc.contributor.referee1.fl_str_mv Carreiro, Luiz Renato Rodrigues
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/0203967709311323
dc.contributor.referee2.fl_str_mv Silva, Regina Cláudia Barbosa da
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/7507421915981968
dc.contributor.referee3.fl_str_mv Ribeiro, Miriam Oliveira
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/7069953370349465
dc.contributor.referee4.fl_str_mv Scorza, Fulvio Alexandre
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/3665794780601169
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8835810156810156
dc.contributor.author.fl_str_mv Pimentel, Luciana Cristina
contributor_str_mv Cysneiros, Roberta Monterazzo
Carreiro, Luiz Renato Rodrigues
Silva, Regina Cláudia Barbosa da
Ribeiro, Miriam Oliveira
Scorza, Fulvio Alexandre
dc.subject.por.fl_str_mv pilocarpina
TDAH
epilepsia
receptor dopaminérgico
topic pilocarpina
TDAH
epilepsia
receptor dopaminérgico
CNPQ::CIENCIAS DA SAUDE::FARMACIA
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::FARMACIA
description The pilocarpine model of Temporal Lobe Epilepsy (TLE) reliably reproduces the characteristics found in TLE in humans and provokes Attention-deficit/hyperactivity disorder (ADHD)-like behaviors in rodents. However, it is not known if these behavioral changes are associated with variations on genetic expression. The present study aimed to investigate behavior patterns and molecular indicators of ADHD in the pilocarpine model of TLE. Male Wistar rats at 25 day of age were submitted to animal model of TLE by pilocarpine injection (350 mg/kg, ip) and a control group received saline 0.9%. The behavioural tests (open field and operant conditioning box) started from 28 days postnatal. Through Real-Time Polimerase Chain Reaction (RT-PCR), were evaluated the expression of somatostatin, mGluR7 and dopaminergic receptors subtype D1 and subtype D5, in the pre-frontal cortex and hippocampus. Behavioral parameters were analysed using Mixed ANOVA, followed by Bonferroni for post-hoc testing. For data analyses of gene expression, t-Student test was used. The data were expressed as mean ± standard error and p-values of 0.05 or less were considered significant. The analyses were effectuated using commercial program (Prism 5.03 for windows). Results in open field for total locomotion revealed a significant difference between groups (F[1,144]=9,32 p=0,0076) and between sessions (F[9,144]= 5,74 p<0,0001), nor effect of interaction between factors (F[9,144]=9,32 NS); and for central locomotion, in percentage, was a significantly diferente between groups (F[1,144]=5,54 p=0,031), effect of interaction between the factors (F[9,144]=3,41 p=0,0008), with no difference between sessions (F[9,144]=0,75 NS). In Skinner box, no significant differences were found between the groups in experimental conditions of this study. For RT-PCR there were observed no significant differences in the expression relative of mRNA in the analyzed genes. We concluded that animals with TLE exhibited elevated locomotor activity and reduced level of anxiety-related behavior. There was observed no deficit of attention and impulsive-like behavior. There were found no variations for somatostatin gene expression, mGluR7 and dopaminergic receptors D1 and D5, in prefrontal cortex and in hippocampus. Behavioral alterations observed in the model of TLE probably are not related to gene alterations of somatostatin and these receptors.
publishDate 2017
dc.date.accessioned.fl_str_mv 2017-04-03T13:31:25Z
2020-05-28T18:09:22Z
dc.date.issued.fl_str_mv 2017-02-09
dc.date.available.fl_str_mv 2020-05-28T18:09:22Z
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.citation.fl_str_mv PIMENTEL, Luciana Cristina. Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal. 2017. 89 f. Tese( Distúrbios do Desenvolvimento) - Universidade Presbiteriana Mackenzie, São Paulo.
dc.identifier.uri.fl_str_mv http://dspace.mackenzie.br/handle/10899/24549
identifier_str_mv PIMENTEL, Luciana Cristina. Avaliação comportamental e molecular em um modelo de epilepsia do lobo temporal. 2017. 89 f. Tese( Distúrbios do Desenvolvimento) - Universidade Presbiteriana Mackenzie, São Paulo.
url http://dspace.mackenzie.br/handle/10899/24549
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv 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 Presbiteriana Mackenzie
dc.publisher.program.fl_str_mv Distúrbios do Desenvolvimento
dc.publisher.initials.fl_str_mv UPM
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Centro de Ciências Biológicas e da Saúde (CCBS)
publisher.none.fl_str_mv Universidade Presbiteriana Mackenzie
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações do Mackenzie
instname:Universidade Presbiteriana Mackenzie (MACKENZIE)
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instname_str Universidade Presbiteriana Mackenzie (MACKENZIE)
instacron_str MACKENZIE
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reponame_str Biblioteca Digital de Teses e Dissertações do Mackenzie
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