Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal

Detalhes bibliográficos
Ano de defesa: 2022
Autor(a) principal: Marques, Bruno Lemes lattes
Orientador(a): Pinto, Mauro Cunha Xavier lattes
Banca de defesa: Pinto, Mauro Cunha Xavier, Vitorino, Fernanda Giachini, Castro, Célio José de
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Goiás
Programa de Pós-Graduação: Programa de Pós-graduação em Ciências Biológicas (ICB)
Departamento: Instituto de Ciências Biológicas - ICB (RMG)
País: Brasil
Palavras-chave em Português:
Neuroproteção
Sarcosina
Isquemia
Palavras-chave em Inglês:
Neuroprotection
Sarcosine
Schemia
Área do conhecimento CNPq:
CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA GERAL
Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/12501
Resumo: Stroke is characterized by a disruption in the cerebral blood supply, leading to oxygen and glucose deprivation to the tissue. Cerebral ischemia involves enhanced glutamate release, abnormal NMDAR activation, and excitotoxicity. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission through NMDA receptors, suggesting an alternative stroke therapeutic strategy. This work investigated the neuroprotective and neurorestorative potential of GlyT1 inhibition in a mouse model of focal ischemia. Swiss mice subjected to permanent middle cerebral artery occlusion (MCAO) were randomized to receive three different doses of Sarcosine (125, 250, and 500 mg/kg) or vehicle before or after ischemia. Pretreatment with 250 and 500 mg/kg of Sarcosine led to neuroprotection against stroke, as demonstrated by reduction of infarct area and neurological deficits. Moreover, GluN2A/CaMKIV/CREB and BDNF/TrKB/Akt/mTOR pathways were enhanced by sarcosine. The sarcosine neuroprotection is also related to GluN2B subunit downregulation and a decrease in CaMKIIα phosphorylation. Additionally, we observed that post-stroke treatment with higher doses of Sarcosine improves the neurorepair process, which is evidenced by the marked reduction of the infarct area and motor deficits. Therefore, sarcosine pretreatment induced neuroprotection through the BDNF/TRKB and CaMKIV/CREB pathways, both processes trigged by NMDAR activity.
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spelling Pinto, Mauro Cunha Xavierhttp://lattes.cnpq.br/0868250984727943Pinto, Mauro Cunha XavierVitorino, Fernanda GiachiniCastro, Célio José dehttp://lattes.cnpq.br/0376107627751138Marques, Bruno Lemes2022-12-15T14:24:23Z2022-12-15T14:24:23Z2022-11-04MARQUES, B. L. Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal. 2022. 60 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2022.http://repositorio.bc.ufg.br/tede/handle/tede/12501Stroke is characterized by a disruption in the cerebral blood supply, leading to oxygen and glucose deprivation to the tissue. Cerebral ischemia involves enhanced glutamate release, abnormal NMDAR activation, and excitotoxicity. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission through NMDA receptors, suggesting an alternative stroke therapeutic strategy. This work investigated the neuroprotective and neurorestorative potential of GlyT1 inhibition in a mouse model of focal ischemia. Swiss mice subjected to permanent middle cerebral artery occlusion (MCAO) were randomized to receive three different doses of Sarcosine (125, 250, and 500 mg/kg) or vehicle before or after ischemia. Pretreatment with 250 and 500 mg/kg of Sarcosine led to neuroprotection against stroke, as demonstrated by reduction of infarct area and neurological deficits. Moreover, GluN2A/CaMKIV/CREB and BDNF/TrKB/Akt/mTOR pathways were enhanced by sarcosine. The sarcosine neuroprotection is also related to GluN2B subunit downregulation and a decrease in CaMKIIα phosphorylation. Additionally, we observed that post-stroke treatment with higher doses of Sarcosine improves the neurorepair process, which is evidenced by the marked reduction of the infarct area and motor deficits. Therefore, sarcosine pretreatment induced neuroprotection through the BDNF/TRKB and CaMKIV/CREB pathways, both processes trigged by NMDAR activity.O AVE (Acidente Vascular Encefálico) é caracterizado por uma perturbação no fornecimento de sangue cerebral, levando à privação de oxigênio e glicose ao tecido. A isquemia cerebral envolve uma liberação aumentada de glutamato, ativação anormal de NMDAR (receptores de N-Metil-D-Aspartato), e excitotoxicidade. O transportador de glicina tipo 1 (GlyT1) modula a neurotransmissão glutamatérgica através de receptores NMDA, sugerindo uma estratégia terapêutica alternativa para o AVE. Este trabalho investigou o potencial neuroprotetor e de reparo neuronal da inibição de GlyT1 num modelo de isquemia focal em camundongos. Camundongos Swiss submetidos à oclusão permanente da artéria cerebral média (MCAO) foram randomicamente selecionados para receber três doses diferentes de Sarcosina (125, 250, e 500 mg/kg, injeção intraperitoneal) ou veículo antes ou depois da isquemia. O prétratamento com 250 e 500 mg/kg de sarcosina levou à neuroprotecção contra o AVE, como demonstrado pela redução da área de infarto e déficits neurológicos. Além disso, as vias de GluN2A/CaMKIV/CREB e BDNF/TrKB/Akt/mTOR foram estimuladas pela sarcosina. A neuroproteção da sarcosina está também relacionada com a diminuição da atividade da subunidade GluN2B e com uma diminuição da fosforilação de CaMKIIα. Portanto, a neuroproteção induzida pela sarcosina ocorre através da via de BDNF/TRKB e CaMKIV/CREB, ambos os processos desencadeados pela atividade de NMDAR.Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2022-12-13T18:59:36Z No. of bitstreams: 2 Dissertação - Bruno Lemes Marques - 2022.pdf: 3550357 bytes, checksum: dda739526143f991ca6ffa0e38ecbaa5 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2022-12-15T14:24:23Z (GMT) No. of bitstreams: 2 Dissertação - Bruno Lemes Marques - 2022.pdf: 3550357 bytes, checksum: dda739526143f991ca6ffa0e38ecbaa5 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Made available in DSpace on 2022-12-15T14:24:23Z (GMT). No. of bitstreams: 2 Dissertação - Bruno Lemes Marques - 2022.pdf: 3550357 bytes, checksum: dda739526143f991ca6ffa0e38ecbaa5 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5) Previous issue date: 2022-11-04Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Biológicas (ICB)UFGBrasilInstituto de Ciências Biológicas - ICB (RMG)Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessNeuroproteçãoSarcosinaIsquemiaNeuroprotectionSarcosineSchemiaCIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA GERALEfeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focalNeuroprotective effect of sarcosine in an animal model of focal brain ischemiainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis15500500500500235241reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.bc.ufg.br/tede/bitstreams/50e4a430-1532-49cd-8a07-20b650e334fb/download4460e5956bc1d1639be9ae6146a50347MD52ORIGINALDissertação - Bruno Lemes Marques - 2022.pdfDissertação - Bruno Lemes Marques - 2022.pdfapplication/pdf3550357http://repositorio.bc.ufg.br/tede/bitstreams/433427a2-3ebd-4b9d-81f2-4f2d0abbd951/downloaddda739526143f991ca6ffa0e38ecbaa5MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.bc.ufg.br/tede/bitstreams/5b2a136d-78fa-4d3a-87e4-0486b2e85d74/download8a4605be74aa9ea9d79846c1fba20a33MD51tede/125012022-12-15 11:24:23.375http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accessoai:repositorio.bc.ufg.br:tede/12501http://repositorio.bc.ufg.br/tedeRepositório InstitucionalPUBhttp://repositorio.bc.ufg.br/oai/requesttasesdissertacoes.bc@ufg.bropendoar:2022-12-15T14:24:23Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)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
dc.title.pt_BR.fl_str_mv Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
dc.title.alternative.eng.fl_str_mv Neuroprotective effect of sarcosine in an animal model of focal brain ischemia
title Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
spellingShingle Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
Marques, Bruno Lemes
Neuroproteção
Sarcosina
Isquemia
Neuroprotection
Sarcosine
Schemia
CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA GERAL
title_short Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
title_full Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
title_fullStr Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
title_full_unstemmed Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
title_sort Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
author Marques, Bruno Lemes
author_facet Marques, Bruno Lemes
author_role author
dc.contributor.advisor1.fl_str_mv Pinto, Mauro Cunha Xavier
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0868250984727943
dc.contributor.referee1.fl_str_mv Pinto, Mauro Cunha Xavier
dc.contributor.referee2.fl_str_mv Vitorino, Fernanda Giachini
dc.contributor.referee3.fl_str_mv Castro, Célio José de
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0376107627751138
dc.contributor.author.fl_str_mv Marques, Bruno Lemes
contributor_str_mv Pinto, Mauro Cunha Xavier
Pinto, Mauro Cunha Xavier
Vitorino, Fernanda Giachini
Castro, Célio José de
dc.subject.por.fl_str_mv Neuroproteção
Sarcosina
Isquemia
topic Neuroproteção
Sarcosina
Isquemia
Neuroprotection
Sarcosine
Schemia
CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA GERAL
dc.subject.eng.fl_str_mv Neuroprotection
Sarcosine
Schemia
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FARMACOLOGIA::FARMACOLOGIA GERAL
description Stroke is characterized by a disruption in the cerebral blood supply, leading to oxygen and glucose deprivation to the tissue. Cerebral ischemia involves enhanced glutamate release, abnormal NMDAR activation, and excitotoxicity. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission through NMDA receptors, suggesting an alternative stroke therapeutic strategy. This work investigated the neuroprotective and neurorestorative potential of GlyT1 inhibition in a mouse model of focal ischemia. Swiss mice subjected to permanent middle cerebral artery occlusion (MCAO) were randomized to receive three different doses of Sarcosine (125, 250, and 500 mg/kg) or vehicle before or after ischemia. Pretreatment with 250 and 500 mg/kg of Sarcosine led to neuroprotection against stroke, as demonstrated by reduction of infarct area and neurological deficits. Moreover, GluN2A/CaMKIV/CREB and BDNF/TrKB/Akt/mTOR pathways were enhanced by sarcosine. The sarcosine neuroprotection is also related to GluN2B subunit downregulation and a decrease in CaMKIIα phosphorylation. Additionally, we observed that post-stroke treatment with higher doses of Sarcosine improves the neurorepair process, which is evidenced by the marked reduction of the infarct area and motor deficits. Therefore, sarcosine pretreatment induced neuroprotection through the BDNF/TRKB and CaMKIV/CREB pathways, both processes trigged by NMDAR activity.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-12-15T14:24:23Z
dc.date.available.fl_str_mv 2022-12-15T14:24:23Z
dc.date.issued.fl_str_mv 2022-11-04
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.citation.fl_str_mv MARQUES, B. L. Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal. 2022. 60 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2022.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/12501
identifier_str_mv MARQUES, B. L. Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal. 2022. 60 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Goiás, Goiânia, 2022.
url http://repositorio.bc.ufg.br/tede/handle/tede/12501
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 15
dc.relation.confidence.fl_str_mv 500
500
500
500
dc.relation.department.fl_str_mv 23
dc.relation.cnpq.fl_str_mv 524
dc.relation.sponsorship.fl_str_mv 1
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.publisher.none.fl_str_mv Universidade Federal de Goiás
dc.publisher.program.fl_str_mv Programa de Pós-graduação em Ciências Biológicas (ICB)
dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Instituto de Ciências Biológicas - ICB (RMG)
publisher.none.fl_str_mv Universidade Federal de Goiás
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFG
instname:Universidade Federal de Goiás (UFG)
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reponame_str Repositório Institucional da UFG
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