Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos

Detalhes bibliográficos
Autor(a) principal: Gois, Auderlan Mendonça de
Data de Publicação: 2016
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: https://ri.ufs.br/handle/riufs/3988
Resumo: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects the somatic motor system through the degeneration of upper and lower motors neurons. Evidence suggests that the cerebrospinal fluid (CSF), which is in direct contact with the nervous system, has soluble substance that could cause injuries in motor neurons. Animal models that express mutant ALS associated genes have been created to study the various etiopathological mechanisms which manifest themselves similarly to that occur in ALS patients. However, these models best represent the etiology of the disease in familiar cases and there is not yet an animal model that represents the characteristics of the disease in sporadic form, despite the similarity between familiar and sporadic cases. Thus, the aim of this study was to evaluate the motor and histological changes after intracerebroventricular injection (i.c.v.) of CSF from ALS sporadic patients in rats. 43 seven-month-old Wistar rats were used, coming from the sectoral animal facility of the Department of Physiology at the Federal University of Sergipe. The study was divided into two experiments: (I) with a single administration i.c.v. of the CSF and (II) with repeated administration i.c.v. of the CSF. In the experiment I, the animals were divided into 3 groups: control (CTR, artificial CSF solution), non-ALS (N-ALS, CSF of patients without neurological disease) and ALS (ALS, LCR of patients with sporadic ALS) who received a single injection i.c.v. (7.5μL) and one week after were subjected to motor tests: strength test, catalepsy test, open field test and walking test once a week for 30 days. In the Experiment II, animals were divided into 3 groups: control (CTR) Non-ALS (N-ALS) and ALS and they received daily injection for 6 days, i.c.v. (5.0μL). Throughout the treatment the animals underwent the motor tests already mentioned. After the tests, in both experiments, rats were anesthetized, perfused, their spinal cords were removed and subjected to histological analysis by hematoxylin-eosin for general morphological observation. In the first experiment ,in ALS group, motor alteration was observed in the strength test, open field and in the walking test, accompanied by a reduction of motor neurons and glial cells in the thoracic and lumbar regions of the spinal cord. In the second experiment, Also in the ALS group, it was observed driving change in catalepsy, open field and in the walking test, accompanied by an increase of glial cells in the lumbar region of the spinal cord. Data presented in this study show that the CSF management of ALS patients can cause pathogenic mechanisms similar to those seen in humans and other animal models of ALS.
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spelling Gois, Auderlan Mendonça deSantos, José Ronaldo dosMendonça, Deise Maria Furtado dehttp://lattes.cnpq.br/34689247147138902017-09-26T12:31:19Z2017-09-26T12:31:19Z2016-02-26Gois, Auderlan Mendonça de. Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos. 2016. 91 f. Dissertação (Pós-Graduação em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, 2016.https://ri.ufs.br/handle/riufs/3988Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects the somatic motor system through the degeneration of upper and lower motors neurons. Evidence suggests that the cerebrospinal fluid (CSF), which is in direct contact with the nervous system, has soluble substance that could cause injuries in motor neurons. Animal models that express mutant ALS associated genes have been created to study the various etiopathological mechanisms which manifest themselves similarly to that occur in ALS patients. However, these models best represent the etiology of the disease in familiar cases and there is not yet an animal model that represents the characteristics of the disease in sporadic form, despite the similarity between familiar and sporadic cases. Thus, the aim of this study was to evaluate the motor and histological changes after intracerebroventricular injection (i.c.v.) of CSF from ALS sporadic patients in rats. 43 seven-month-old Wistar rats were used, coming from the sectoral animal facility of the Department of Physiology at the Federal University of Sergipe. The study was divided into two experiments: (I) with a single administration i.c.v. of the CSF and (II) with repeated administration i.c.v. of the CSF. In the experiment I, the animals were divided into 3 groups: control (CTR, artificial CSF solution), non-ALS (N-ALS, CSF of patients without neurological disease) and ALS (ALS, LCR of patients with sporadic ALS) who received a single injection i.c.v. (7.5μL) and one week after were subjected to motor tests: strength test, catalepsy test, open field test and walking test once a week for 30 days. In the Experiment II, animals were divided into 3 groups: control (CTR) Non-ALS (N-ALS) and ALS and they received daily injection for 6 days, i.c.v. (5.0μL). Throughout the treatment the animals underwent the motor tests already mentioned. After the tests, in both experiments, rats were anesthetized, perfused, their spinal cords were removed and subjected to histological analysis by hematoxylin-eosin for general morphological observation. In the first experiment ,in ALS group, motor alteration was observed in the strength test, open field and in the walking test, accompanied by a reduction of motor neurons and glial cells in the thoracic and lumbar regions of the spinal cord. In the second experiment, Also in the ALS group, it was observed driving change in catalepsy, open field and in the walking test, accompanied by an increase of glial cells in the lumbar region of the spinal cord. Data presented in this study show that the CSF management of ALS patients can cause pathogenic mechanisms similar to those seen in humans and other animal models of ALS.A Esclerose Lateral Amiotrófica (ELA) é uma doença neurodegenerativa progressiva, que afeta o sistema motor somático através da degeneração dos neurônios motores superiores e inferiores. Evidências apontam que o líquido cefalorraquidiano (LCR), que está em íntimo contato com o sistema nervoso, apresenta substâncias solúveis que podem provocar lesões em neurônios motores. Modelos animais que expressam genes mutantes associados à ELA foram desenvolvidos, para o estudo dos mais diversos mecanismos etiopatológicos que se manifestam de forma similar aos que ocorrem em pacientes com a doença. Entretanto, esses modelos representam melhor a etiologia da doença em casos familiares e, apesar da semelhança entre casos familiares e esporádicos, ainda não se tem um modelo animal que represente características da doença nesta última. Diante disso, o objetivo do presente trabalho foi avaliar as alterações motoras e histológicas após injeção intracerebroventricular (i.c.v.) de LCR de pacientes com ELA esporádica em ratos Wistar. Foram ultilizados 43 ratos Wistar, com idade aproximada de sete meses, provenientes do Biotério Setorial do Departamento de Fisiologia da Universidade Federal de Sergipe. O trabalho foi dividido em 2 experimentos: (I) com uma única administração i.c.v. de LCR e (II) com administrações repetidas i.c.v. de LCR. No experimento I os animais foram divididos em 3 grupos, controle (CTR, solução de LCR artificial), não-ELA (NELA, LCR de pacientes sem doenças neurológicas) e ELA (ELA, LCR de paciente com ELA esporádica) que receberam uma única injeção i.c.v. de 7,5 μL e após uma semana foram submetidos aos testes motores: teste de força, catalepsia, campo aberto e teste de marcha uma vez por semana durante 30 dias. No experimento II, os animais foram divididos em 3 grupos, controle (CTR), Não-ELA (N-ELA) e ELA que receberam uma injeção diária, durante 6 dias, i.c.v. de 5 μL. Ao longo do tratamento, os animais foram submetidos aos testes motores acima mencionados. Após os testes, em ambos experimentos, os ratos foram anestesiados, perfundidos, suas medulas removidas e submetidas à análise histológica pela coloração de hematoxilina-eosina para observação morfológica geral. No experimento I, no grupo ELA, foi observado alteração motora no teste de força, campo aberto e no teste de marcha, acompanhado por uma redução de neurônios motores e células gliais na região torácica e lombar da medula espinal. No experimento II, também no grupo ELA, foi observado alteração motora na catalepsia, campo aberto e no teste de marcha, acompanhado de um aumento de células gliais na região lombar da medula espinal. Os dados apresentados neste estudo mostram que a administração de LCR de pacientes com ELA pode provocar mecanismos patogênicos semelhantes aos observados em humanos e outros modelos animais de ELA.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade Federal de SergipePós-Graduação em Ciências FisiológicasUFSBrasilFisiologiaSistema nervosoDegeneração do sistema nervosoEsclerose lateral amiotróficaLíquido cefalorraquidianoDoenças neuromuscularesDoenças neurodegenerativasDoença do neurônio motorInjeção intracerebroventricularModelo animalNeurodegenerative diseasesMotor neuron diseaseIntracerebroventricular injectionAnimal modelCIENCIAS BIOLOGICAS::FISIOLOGIAAlterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratosMotor, behavioral and histopathological changes after intracerebroventricular cerebrospinal fluid injection of patients with amyotrophic lateral sclerosis in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSORIGINALAUDERLAN_MENDONCA_GOIS.pdfapplication/pdf3265835https://ri.ufs.br/jspui/bitstream/riufs/3988/1/AUDERLAN_MENDONCA_GOIS.pdf265cc40c683649576d3d6e4418074c58MD51TEXTAUDERLAN_MENDONCA_GOIS.pdf.txtAUDERLAN_MENDONCA_GOIS.pdf.txtExtracted texttext/plain153962https://ri.ufs.br/jspui/bitstream/riufs/3988/2/AUDERLAN_MENDONCA_GOIS.pdf.txta55cfd95ba8c3727744365be5a5681afMD52THUMBNAILAUDERLAN_MENDONCA_GOIS.pdf.jpgAUDERLAN_MENDONCA_GOIS.pdf.jpgGenerated Thumbnailimage/jpeg1339https://ri.ufs.br/jspui/bitstream/riufs/3988/3/AUDERLAN_MENDONCA_GOIS.pdf.jpg981efcebcf9f1581cec8dbb5adc351fcMD53riufs/39882017-11-24 21:44:18.993oai:ufs.br:riufs/3988Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2017-11-25T00:44:18Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.por.fl_str_mv Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos
dc.title.alternative.eng.fl_str_mv Motor, behavioral and histopathological changes after intracerebroventricular cerebrospinal fluid injection of patients with amyotrophic lateral sclerosis in rats
title Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos
spellingShingle Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos
Gois, Auderlan Mendonça de
Fisiologia
Sistema nervoso
Degeneração do sistema nervoso
Esclerose lateral amiotrófica
Líquido cefalorraquidiano
Doenças neuromusculares
Doenças neurodegenerativas
Doença do neurônio motor
Injeção intracerebroventricular
Modelo animal
Neurodegenerative diseases
Motor neuron disease
Intracerebroventricular injection
Animal model
CIENCIAS BIOLOGICAS::FISIOLOGIA
title_short Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos
title_full Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos
title_fullStr Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos
title_full_unstemmed Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos
title_sort Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos
author Gois, Auderlan Mendonça de
author_facet Gois, Auderlan Mendonça de
author_role author
dc.contributor.author.fl_str_mv Gois, Auderlan Mendonça de
dc.contributor.advisor1.fl_str_mv Santos, José Ronaldo dos
dc.contributor.advisor-co1.fl_str_mv Mendonça, Deise Maria Furtado de
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/3468924714713890
contributor_str_mv Santos, José Ronaldo dos
Mendonça, Deise Maria Furtado de
dc.subject.por.fl_str_mv Fisiologia
Sistema nervoso
Degeneração do sistema nervoso
Esclerose lateral amiotrófica
Líquido cefalorraquidiano
Doenças neuromusculares
Doenças neurodegenerativas
Doença do neurônio motor
Injeção intracerebroventricular
Modelo animal
topic Fisiologia
Sistema nervoso
Degeneração do sistema nervoso
Esclerose lateral amiotrófica
Líquido cefalorraquidiano
Doenças neuromusculares
Doenças neurodegenerativas
Doença do neurônio motor
Injeção intracerebroventricular
Modelo animal
Neurodegenerative diseases
Motor neuron disease
Intracerebroventricular injection
Animal model
CIENCIAS BIOLOGICAS::FISIOLOGIA
dc.subject.eng.fl_str_mv Neurodegenerative diseases
Motor neuron disease
Intracerebroventricular injection
Animal model
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA
description Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects the somatic motor system through the degeneration of upper and lower motors neurons. Evidence suggests that the cerebrospinal fluid (CSF), which is in direct contact with the nervous system, has soluble substance that could cause injuries in motor neurons. Animal models that express mutant ALS associated genes have been created to study the various etiopathological mechanisms which manifest themselves similarly to that occur in ALS patients. However, these models best represent the etiology of the disease in familiar cases and there is not yet an animal model that represents the characteristics of the disease in sporadic form, despite the similarity between familiar and sporadic cases. Thus, the aim of this study was to evaluate the motor and histological changes after intracerebroventricular injection (i.c.v.) of CSF from ALS sporadic patients in rats. 43 seven-month-old Wistar rats were used, coming from the sectoral animal facility of the Department of Physiology at the Federal University of Sergipe. The study was divided into two experiments: (I) with a single administration i.c.v. of the CSF and (II) with repeated administration i.c.v. of the CSF. In the experiment I, the animals were divided into 3 groups: control (CTR, artificial CSF solution), non-ALS (N-ALS, CSF of patients without neurological disease) and ALS (ALS, LCR of patients with sporadic ALS) who received a single injection i.c.v. (7.5μL) and one week after were subjected to motor tests: strength test, catalepsy test, open field test and walking test once a week for 30 days. In the Experiment II, animals were divided into 3 groups: control (CTR) Non-ALS (N-ALS) and ALS and they received daily injection for 6 days, i.c.v. (5.0μL). Throughout the treatment the animals underwent the motor tests already mentioned. After the tests, in both experiments, rats were anesthetized, perfused, their spinal cords were removed and subjected to histological analysis by hematoxylin-eosin for general morphological observation. In the first experiment ,in ALS group, motor alteration was observed in the strength test, open field and in the walking test, accompanied by a reduction of motor neurons and glial cells in the thoracic and lumbar regions of the spinal cord. In the second experiment, Also in the ALS group, it was observed driving change in catalepsy, open field and in the walking test, accompanied by an increase of glial cells in the lumbar region of the spinal cord. Data presented in this study show that the CSF management of ALS patients can cause pathogenic mechanisms similar to those seen in humans and other animal models of ALS.
publishDate 2016
dc.date.issued.fl_str_mv 2016-02-26
dc.date.accessioned.fl_str_mv 2017-09-26T12:31:19Z
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dc.identifier.citation.fl_str_mv Gois, Auderlan Mendonça de. Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos. 2016. 91 f. Dissertação (Pós-Graduação em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, 2016.
dc.identifier.uri.fl_str_mv https://ri.ufs.br/handle/riufs/3988
identifier_str_mv Gois, Auderlan Mendonça de. Alterações motoras, comportamentais e histopatológicas após injeção intracerebroventricular de liquor de pacientes com esclerose lateral amiotrófica em ratos. 2016. 91 f. Dissertação (Pós-Graduação em Ciências Fisiológicas) - Universidade Federal de Sergipe, São Cristóvão, 2016.
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