Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/239818 |
Resumo: | Glutaric acidemia type I (GA-I) is an inborn error of metabolism of lysine, hydroxylysine, and tryptophan, caused by glutaryl-CoA-dehydrogenase (GCDH) deficiency, characterized by the buildup of toxic organic acids predominantly in the brain. After acute catabolic states, patients usually develop striatal degeneration, but the mechanisms behind this damage are still unknown. Quinolinic acid (QA), a metabolite of the kynurenine pathway, increases especially during infections/inflammatory processes, and could act synergically with organic acids, contributing to the neurological features of GA-I. The aim of this study was to investigate whether QA increases seizure susceptibility and modifies brain oscillation patterns in an animal model of GA-I, the Gcdh−/− mice taking high-lysine diet (Gcdh−/−-Lys). Therefore, the characteristics of QA-induced seizures and changes in brain oscillatory patterns were evaluated by video-electroencephalography (EEG) analysis recorded in Gcdh−/−-Lys, Gcdh+/+-Lys, and Gcdh−/−-N (normal diet) animals. We found that the number of seizures per animal was similar for all groups receiving QA, Gcdh−/−-Lys-QA, Gcdh+/+-Lys-QA, and Gcdh−/−-N-QA. However, severe seizures were observed in the majority of Gcdh−/−-Lys-QA mice (82%), and only in 25% of Gcdh+/+-Lys-QA and 44% of Gcdh−/−-N-QA mice. All Gcdh−/−-Lys animals developed spontaneous recurrent seizures (SRS), but Gcdh−/−-Lys-QA animals had increased number of SRS, higher mortality rate, and significant predominance of lower frequency oscillations on EEG. Our results suggest that QA plays an important role in the neurological features of GA-I, as Gcdh−/−-Lys mice exhibit increased susceptibility to intrastriatal QA-induced seizures and long-term changes in brain oscillations. |
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Caus, Letícia BarbieriPasquetti, Mayara VendraminSeminotti, BiancaWoontner, MichaelWajner, MoacirCalcagnotto, Maria Elisa2022-06-07T04:40:01Z20220360-4012http://hdl.handle.net/10183/239818001141010Glutaric acidemia type I (GA-I) is an inborn error of metabolism of lysine, hydroxylysine, and tryptophan, caused by glutaryl-CoA-dehydrogenase (GCDH) deficiency, characterized by the buildup of toxic organic acids predominantly in the brain. After acute catabolic states, patients usually develop striatal degeneration, but the mechanisms behind this damage are still unknown. Quinolinic acid (QA), a metabolite of the kynurenine pathway, increases especially during infections/inflammatory processes, and could act synergically with organic acids, contributing to the neurological features of GA-I. The aim of this study was to investigate whether QA increases seizure susceptibility and modifies brain oscillation patterns in an animal model of GA-I, the Gcdh−/− mice taking high-lysine diet (Gcdh−/−-Lys). Therefore, the characteristics of QA-induced seizures and changes in brain oscillatory patterns were evaluated by video-electroencephalography (EEG) analysis recorded in Gcdh−/−-Lys, Gcdh+/+-Lys, and Gcdh−/−-N (normal diet) animals. We found that the number of seizures per animal was similar for all groups receiving QA, Gcdh−/−-Lys-QA, Gcdh+/+-Lys-QA, and Gcdh−/−-N-QA. However, severe seizures were observed in the majority of Gcdh−/−-Lys-QA mice (82%), and only in 25% of Gcdh+/+-Lys-QA and 44% of Gcdh−/−-N-QA mice. All Gcdh−/−-Lys animals developed spontaneous recurrent seizures (SRS), but Gcdh−/−-Lys-QA animals had increased number of SRS, higher mortality rate, and significant predominance of lower frequency oscillations on EEG. Our results suggest that QA plays an important role in the neurological features of GA-I, as Gcdh−/−-Lys mice exhibit increased susceptibility to intrastriatal QA-induced seizures and long-term changes in brain oscillations.application/pdfengJournal of neuroscience research. New York. Vol. 100, no. 4 (Apr. 2022), p. 992-1007Glutaril-coA desidrogenaseÁcido quinolínicoEncéfaloConvulsõesErros inatos do metabolismo dos aminoácidosModelos animaisLisinaBrain oscillationsElectroencephalogramGlutaric acidemia type IQuinolinic acidSeizuresStriatumIncreased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type IEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001141010.pdf.txt001141010.pdf.txtExtracted Texttext/plain75186http://www.lume.ufrgs.br/bitstream/10183/239818/2/001141010.pdf.txt2a90b87b4a877735c09fa8679166fb2aMD52ORIGINAL001141010.pdfTexto completo (inglês)application/pdf2032265http://www.lume.ufrgs.br/bitstream/10183/239818/1/001141010.pdf4d1e41e4dc4fc554eb7fd44b0eb4f66dMD5110183/2398182022-06-08 04:39:35.999209oai:www.lume.ufrgs.br:10183/239818Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-06-08T07:39:35Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I |
title |
Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I |
spellingShingle |
Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I Caus, Letícia Barbieri Glutaril-coA desidrogenase Ácido quinolínico Encéfalo Convulsões Erros inatos do metabolismo dos aminoácidos Modelos animais Lisina Brain oscillations Electroencephalogram Glutaric acidemia type I Quinolinic acid Seizures Striatum |
title_short |
Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I |
title_full |
Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I |
title_fullStr |
Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I |
title_full_unstemmed |
Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I |
title_sort |
Increased susceptibility to quinolinic acid-induced seizures and long-term changes in brain oscillations in an animal model of glutaric acidemia type I |
author |
Caus, Letícia Barbieri |
author_facet |
Caus, Letícia Barbieri Pasquetti, Mayara Vendramin Seminotti, Bianca Woontner, Michael Wajner, Moacir Calcagnotto, Maria Elisa |
author_role |
author |
author2 |
Pasquetti, Mayara Vendramin Seminotti, Bianca Woontner, Michael Wajner, Moacir Calcagnotto, Maria Elisa |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Caus, Letícia Barbieri Pasquetti, Mayara Vendramin Seminotti, Bianca Woontner, Michael Wajner, Moacir Calcagnotto, Maria Elisa |
dc.subject.por.fl_str_mv |
Glutaril-coA desidrogenase Ácido quinolínico Encéfalo Convulsões Erros inatos do metabolismo dos aminoácidos Modelos animais Lisina |
topic |
Glutaril-coA desidrogenase Ácido quinolínico Encéfalo Convulsões Erros inatos do metabolismo dos aminoácidos Modelos animais Lisina Brain oscillations Electroencephalogram Glutaric acidemia type I Quinolinic acid Seizures Striatum |
dc.subject.eng.fl_str_mv |
Brain oscillations Electroencephalogram Glutaric acidemia type I Quinolinic acid Seizures Striatum |
description |
Glutaric acidemia type I (GA-I) is an inborn error of metabolism of lysine, hydroxylysine, and tryptophan, caused by glutaryl-CoA-dehydrogenase (GCDH) deficiency, characterized by the buildup of toxic organic acids predominantly in the brain. After acute catabolic states, patients usually develop striatal degeneration, but the mechanisms behind this damage are still unknown. Quinolinic acid (QA), a metabolite of the kynurenine pathway, increases especially during infections/inflammatory processes, and could act synergically with organic acids, contributing to the neurological features of GA-I. The aim of this study was to investigate whether QA increases seizure susceptibility and modifies brain oscillation patterns in an animal model of GA-I, the Gcdh−/− mice taking high-lysine diet (Gcdh−/−-Lys). Therefore, the characteristics of QA-induced seizures and changes in brain oscillatory patterns were evaluated by video-electroencephalography (EEG) analysis recorded in Gcdh−/−-Lys, Gcdh+/+-Lys, and Gcdh−/−-N (normal diet) animals. We found that the number of seizures per animal was similar for all groups receiving QA, Gcdh−/−-Lys-QA, Gcdh+/+-Lys-QA, and Gcdh−/−-N-QA. However, severe seizures were observed in the majority of Gcdh−/−-Lys-QA mice (82%), and only in 25% of Gcdh+/+-Lys-QA and 44% of Gcdh−/−-N-QA mice. All Gcdh−/−-Lys animals developed spontaneous recurrent seizures (SRS), but Gcdh−/−-Lys-QA animals had increased number of SRS, higher mortality rate, and significant predominance of lower frequency oscillations on EEG. Our results suggest that QA plays an important role in the neurological features of GA-I, as Gcdh−/−-Lys mice exhibit increased susceptibility to intrastriatal QA-induced seizures and long-term changes in brain oscillations. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-06-07T04:40:01Z |
dc.date.issued.fl_str_mv |
2022 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
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http://hdl.handle.net/10183/239818 |
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0360-4012 |
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001141010 |
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0360-4012 001141010 |
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http://hdl.handle.net/10183/239818 |
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eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Journal of neuroscience research. New York. Vol. 100, no. 4 (Apr. 2022), p. 992-1007 |
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openAccess |
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