Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos
Ano de defesa: | 2019 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências da Saúde |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Farmacologia
|
Departamento: |
Farmacologia
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/16448 |
Resumo: | The chronic use of typical antipsychotics has been related to movement disorders development, which are manifested by repetitive, tremors and tardive dyskinesias, manifestations that can reach disabling levels and impair the pharmacological treatment of the original pathology. The aim of the present study was to evaluate magnesium supplementation (Mg; 40 mg / kg, oral, once daily) in prevention (28 days before) and reversion (12 days after), as well as in concomitant supplementation, on haloperidol-induced orofacial dyskinesia (OD) (12 mg / kg; im, once weekly for 4 weeks) in rats. The results showed that the Mg supplementation before, after and concomitant to HAL administration, prevented, reversed and protected from the high vacuous chewing movements frequency (VCM) and cataplepsy. Mg supplementation: i) prevented the generation of reactive species (RS) in cortex and substantias nigra (SN), and reduced the levels of carbonylated proteins (CP) in all evaluated brain areas; ii) reversed RE generation induced by HAL in the cortex and striatum and decreased CP levels in both SN and striatum; iii) prevented RS generation the cortex, striatum and SN, as well as the increased CP levels in SN. From these results, a comparative study between Mg supplementation and nifedipine administration (NIF-10mg / kg / ml, orally, once daily) on the movement disorders induced by HAL in rats was performed sequentially, in order to determine if Mg action is similar to NIF. Both Mg and NIF reduced HAL induced OD. Also, while HAL increased Ca2 + -ATPase activity in the striatum, Mg supplementation reversed it. In the cortex, both Mg and NIF reduced this activity. The immunoreactivity of dopaminergic D1 and D2 receptors and the glutamatergic receptor NMDA were modified in different ways by HAL in the cortex, striatum and SN areas, as well as by the treatments. Of particular importance, was observed the increased immunoreactivity of NMDA receptors in all brain areas being reduced by Mg or NIF in all brain areas analyzed. These findings allow us to propose that Mg may be useful in preventing and minimizing movement disorders induced by classical antipsychotics such as HAL, whose molecular mechanism seems to be involved with a significant and possibly more consistent calcium channel block activity, provided that the group of animals treated with NIF showed less expressive responses when compared to the group treated with Mg. Taken together, the results presented in these studies indicate that Mg supplementation is able to prevent or ameliorate extrapyramidal motor disorders whose mechanism of action seems to be involved in calcium channel blockade. These disorders are often related to chronic antipsychotic treatment, so far there is no effective preventative treatment. Mg supplementation, which is a bivalent cation with low systemic toxicity and low cost, may be an accessible and effective alternative for patients undergoing neuroleptic treatment. |
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2019-05-07T21:06:45Z2019-05-07T21:06:45Z2019-02-08http://repositorio.ufsm.br/handle/1/16448The chronic use of typical antipsychotics has been related to movement disorders development, which are manifested by repetitive, tremors and tardive dyskinesias, manifestations that can reach disabling levels and impair the pharmacological treatment of the original pathology. The aim of the present study was to evaluate magnesium supplementation (Mg; 40 mg / kg, oral, once daily) in prevention (28 days before) and reversion (12 days after), as well as in concomitant supplementation, on haloperidol-induced orofacial dyskinesia (OD) (12 mg / kg; im, once weekly for 4 weeks) in rats. The results showed that the Mg supplementation before, after and concomitant to HAL administration, prevented, reversed and protected from the high vacuous chewing movements frequency (VCM) and cataplepsy. Mg supplementation: i) prevented the generation of reactive species (RS) in cortex and substantias nigra (SN), and reduced the levels of carbonylated proteins (CP) in all evaluated brain areas; ii) reversed RE generation induced by HAL in the cortex and striatum and decreased CP levels in both SN and striatum; iii) prevented RS generation the cortex, striatum and SN, as well as the increased CP levels in SN. From these results, a comparative study between Mg supplementation and nifedipine administration (NIF-10mg / kg / ml, orally, once daily) on the movement disorders induced by HAL in rats was performed sequentially, in order to determine if Mg action is similar to NIF. Both Mg and NIF reduced HAL induced OD. Also, while HAL increased Ca2 + -ATPase activity in the striatum, Mg supplementation reversed it. In the cortex, both Mg and NIF reduced this activity. The immunoreactivity of dopaminergic D1 and D2 receptors and the glutamatergic receptor NMDA were modified in different ways by HAL in the cortex, striatum and SN areas, as well as by the treatments. Of particular importance, was observed the increased immunoreactivity of NMDA receptors in all brain areas being reduced by Mg or NIF in all brain areas analyzed. These findings allow us to propose that Mg may be useful in preventing and minimizing movement disorders induced by classical antipsychotics such as HAL, whose molecular mechanism seems to be involved with a significant and possibly more consistent calcium channel block activity, provided that the group of animals treated with NIF showed less expressive responses when compared to the group treated with Mg. Taken together, the results presented in these studies indicate that Mg supplementation is able to prevent or ameliorate extrapyramidal motor disorders whose mechanism of action seems to be involved in calcium channel blockade. These disorders are often related to chronic antipsychotic treatment, so far there is no effective preventative treatment. Mg supplementation, which is a bivalent cation with low systemic toxicity and low cost, may be an accessible and effective alternative for patients undergoing neuroleptic treatment.O uso crônico de antipsicóticos típicos têm sido relacionados ao desenvolvimento de distúrbios do movimento, que se manifestam por movimentos involuntários repetitivos, tremores e discinesia tardia, manifestações que podem atingir níveis incapacitantes, prejudicando o tratamento farmacológico da patologia original. O objetivo inicial do presente estudo foi investigar a influência da suplementação de magnésio (Mg) (Mg; 40 mg / kg, via oral, uma vez ao dia) na prevenção (28 dias antes) e reversão (12 dias após), como também em suplementação concomitante, sobre a discinesia orofacial (DO) induzida por haloperidol (HAL) (12 mg / kg; im, uma vez por semana, durante 4 semanas) em ratos. Os resultados mostraram que a suplementação de Mg antes, após e concomitante à administração de HAL, respectivamente impediu, reverteu e preveniu o aumento da frequência dos movimentos de mascar no vazio (MMV) e cataplepsia. A suplementação de Mg: i) impediu a geração de espécies reativas (ER) em ambos córtex e substantia nigra (SN), reduzindo os níveis de proteínas carboniladas (PC) em todas as áreas cerebrais avaliadas; ii) reverteu a geração de ER induzida pelo HAL em ambos córtex e no estriado, diminuindo os níveis de PC em ambos SN e estriado; iii) preveniu a geração de ER no córtex, estriado e SN, como também o aumento dos níveis de PC na SN. A partir destes resultados, foi realizado sequencialmente um estudo comparativo entre a suplementação de Mg e a administração de nifedipina (NIF- 10mg/Kg/mL, via oral, uma vez ao dia), sobre os distúrbios do movimento induzidos pelo HAL em ratos, afim de determinar se ação do Mg é semelhante a NIF. Ambos Mg e NIF reduziram a DO induzida pelo HAL. Também, enquanto o HAL aumentou a atividade da Ca2+-ATPase no estriado, a suplementação de Mg reverteu. No córtex, tanto o Mg quanto a NIF reduziram tal atividade. A imunorreatividade dos receptores dopaminérgicos D1 e D2 e do receptor glutamatérgico NMDA, foram modificadas de diferentes maneiras pelo HAL nas áreas do córtex, estriado e SN, como também pelos tratamentos. De particular importância observou-se o aumento da imunorreatividade dos receptores NMDA em todas as regiões cerebrais sendo reduzidas pelo Mg ou NIF em todas as regiões analisadas. Esses achados nos permitem propor que o Mg pode ser útil para prevenir e minimizar distúrbios de movimento induzidos por antipsicóticos clássicos como o HAL, cujo mecanismo molecular parece estar envolvido com um significativo e possivelmente mais consistente bloqueio dos canais de cálcio, desde que o grupo de animais tratados com NIF apresentou respostas menos expressivas quando comparados ao grupo tratado com Mg. Em conjunto, os resultados apresentados nestes estudos indicam que a suplementação de Mg é capaz de prevenir ou amenizar distúrbios motores extrapiramidais, cujo mecanismo de ação parece estar envolvido no bloqueio de canais de cálcio. Estes distúrbios são frequentemente relacionados com o tratamento crônico antipsicótico, não existindo até o momento um tratamento preventivo eficaz. A suplementação de Mg, sendo um cátion bivalente de baixa toxicidade sistêmica e de baixo custo, pode significar uma alternativa acessível e eficaz para os pacientes sob tratamento neuroléptico.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessDiscinesia orofacialHaloperidolDistúrbios do movimentoMg2+CatalepsiaDano oxidativoNifedipinaCálcioReceptor NMDAOrofacial dyskinesiaMovement disordersCatalepsyOxidative damageNifedipineCalciumNMDA receptorCNPQ::CIENCIAS DA SAUDE::FARMACIAAspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratosBehavioral, biochemical and molecular aspects of magnesium role involved in motor disorders experimentally induced in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBurger, Marilise Escobarhttp://lattes.cnpq.br/9128090974948413Brüning, César Augustohttp://lattes.cnpq.br/6471517217246368Benvegnú, Dalila Moterhttp://lattes.cnpq.br/6134516963963514Oliveira, Mauro Schneiderhttp://lattes.cnpq.br/7132934163734175Fachinetto, Roseleihttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2http://lattes.cnpq.br/6542763052639972Kronbauer, Maikel4003000000056006efd884c-d094-402e-93e9-92619b27afc113af70d2-1601-4f04-b37e-6343f953ad08264d170b-fa65-457a-ab0a-b44bf3cfb243fcf10e76-96ec-4734-88db-458167adfddddf67a9a8-bb2b-4fe4-b1ab-0baffdb61ead47851031-d698-41a7-a810-90b77c6b42e8reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGFARMACOLOGIA_2019_KRONBAUER_MAIKEL.pdfTES_PPGFARMACOLOGIA_2019_KRONBAUER_MAIKEL.pdfTese de Doutoradoapplication/pdf5956776http://repositorio.ufsm.br/bitstream/1/16448/1/TES_PPGFARMACOLOGIA_2019_KRONBAUER_MAIKEL.pdfb07038722425e3b6ca3a4f66360f4d02MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos |
dc.title.alternative.eng.fl_str_mv |
Behavioral, biochemical and molecular aspects of magnesium role involved in motor disorders experimentally induced in rats |
title |
Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos |
spellingShingle |
Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos Kronbauer, Maikel Discinesia orofacial Haloperidol Distúrbios do movimento Mg2+ Catalepsia Dano oxidativo Nifedipina Cálcio Receptor NMDA Orofacial dyskinesia Movement disorders Catalepsy Oxidative damage Nifedipine Calcium NMDA receptor CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos |
title_full |
Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos |
title_fullStr |
Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos |
title_full_unstemmed |
Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos |
title_sort |
Aspectos comportamentais, bioquímicos e moleculares implicados no papel do magnésio nos distúrbios motores induzidos experimentalmente em ratos |
author |
Kronbauer, Maikel |
author_facet |
Kronbauer, Maikel |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Burger, Marilise Escobar |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9128090974948413 |
dc.contributor.referee1.fl_str_mv |
Brüning, César Augusto |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/6471517217246368 |
dc.contributor.referee2.fl_str_mv |
Benvegnú, Dalila Moter |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/6134516963963514 |
dc.contributor.referee3.fl_str_mv |
Oliveira, Mauro Schneider |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/7132934163734175 |
dc.contributor.referee4.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.referee4Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/6542763052639972 |
dc.contributor.author.fl_str_mv |
Kronbauer, Maikel |
contributor_str_mv |
Burger, Marilise Escobar Brüning, César Augusto Benvegnú, Dalila Moter Oliveira, Mauro Schneider Fachinetto, Roselei |
dc.subject.por.fl_str_mv |
Discinesia orofacial Haloperidol Distúrbios do movimento Mg2+ Catalepsia Dano oxidativo Nifedipina Cálcio Receptor NMDA |
topic |
Discinesia orofacial Haloperidol Distúrbios do movimento Mg2+ Catalepsia Dano oxidativo Nifedipina Cálcio Receptor NMDA Orofacial dyskinesia Movement disorders Catalepsy Oxidative damage Nifedipine Calcium NMDA receptor CNPQ::CIENCIAS DA SAUDE::FARMACIA |
dc.subject.eng.fl_str_mv |
Orofacial dyskinesia Movement disorders Catalepsy Oxidative damage Nifedipine Calcium NMDA receptor |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
The chronic use of typical antipsychotics has been related to movement disorders development, which are manifested by repetitive, tremors and tardive dyskinesias, manifestations that can reach disabling levels and impair the pharmacological treatment of the original pathology. The aim of the present study was to evaluate magnesium supplementation (Mg; 40 mg / kg, oral, once daily) in prevention (28 days before) and reversion (12 days after), as well as in concomitant supplementation, on haloperidol-induced orofacial dyskinesia (OD) (12 mg / kg; im, once weekly for 4 weeks) in rats. The results showed that the Mg supplementation before, after and concomitant to HAL administration, prevented, reversed and protected from the high vacuous chewing movements frequency (VCM) and cataplepsy. Mg supplementation: i) prevented the generation of reactive species (RS) in cortex and substantias nigra (SN), and reduced the levels of carbonylated proteins (CP) in all evaluated brain areas; ii) reversed RE generation induced by HAL in the cortex and striatum and decreased CP levels in both SN and striatum; iii) prevented RS generation the cortex, striatum and SN, as well as the increased CP levels in SN. From these results, a comparative study between Mg supplementation and nifedipine administration (NIF-10mg / kg / ml, orally, once daily) on the movement disorders induced by HAL in rats was performed sequentially, in order to determine if Mg action is similar to NIF. Both Mg and NIF reduced HAL induced OD. Also, while HAL increased Ca2 + -ATPase activity in the striatum, Mg supplementation reversed it. In the cortex, both Mg and NIF reduced this activity. The immunoreactivity of dopaminergic D1 and D2 receptors and the glutamatergic receptor NMDA were modified in different ways by HAL in the cortex, striatum and SN areas, as well as by the treatments. Of particular importance, was observed the increased immunoreactivity of NMDA receptors in all brain areas being reduced by Mg or NIF in all brain areas analyzed. These findings allow us to propose that Mg may be useful in preventing and minimizing movement disorders induced by classical antipsychotics such as HAL, whose molecular mechanism seems to be involved with a significant and possibly more consistent calcium channel block activity, provided that the group of animals treated with NIF showed less expressive responses when compared to the group treated with Mg. Taken together, the results presented in these studies indicate that Mg supplementation is able to prevent or ameliorate extrapyramidal motor disorders whose mechanism of action seems to be involved in calcium channel blockade. These disorders are often related to chronic antipsychotic treatment, so far there is no effective preventative treatment. Mg supplementation, which is a bivalent cation with low systemic toxicity and low cost, may be an accessible and effective alternative for patients undergoing neuroleptic treatment. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-05-07T21:06:45Z |
dc.date.available.fl_str_mv |
2019-05-07T21:06:45Z |
dc.date.issued.fl_str_mv |
2019-02-08 |
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.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/16448 |
url |
http://repositorio.ufsm.br/handle/1/16448 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
400300000005 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
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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 |
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Universidade Federal de Santa Maria Centro de Ciências da Saúde |
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Programa de Pós-Graduação em Farmacologia |
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UFSM |
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Brasil |
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Farmacologia |
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Universidade Federal de Santa Maria Centro de Ciências da Saúde |
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