Efeito neuroprotetor da sarcosina em modelo animal de isquemia cerebral focal
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
dARK ID: | ark:/38995/0013000002jg6 |
Texto Completo: | 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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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/12501ark:/38995/0013000002jg6Stroke 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 |
dc.identifier.dark.fl_str_mv |
ark:/38995/0013000002jg6 |
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. ark:/38995/0013000002jg6 |
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) |
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UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Instituto de Ciências Biológicas - ICB (RMG) |
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Universidade Federal de Goiás |
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