Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas

Detalhes bibliográficos
Autor(a) principal: Gutierres, Jessié Martins
Data de Publicação: 2013
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
dARK ID: ark:/26339/00130000066jv
Texto Completo: http://repositorio.ufsm.br/handle/1/4479
Resumo: Dementia is a brain disorder characterized by decline in several mental functions and results in deficits in memory functioning in a variety of cognitive tasks. Evidence has emerged showing that anthocyanins (ANT) possess antioxidant, vasodilator and neuroprotective properties, and more recently are able to improve memory. The aim of our study was to investigate the role of ANT on memory and relate these changes to the cholinergic and purinergic in a model of amnesia induced by scopolamine (SCO), in a model of sporadic dementia of the Alzheimer type (SDAT), induced by intracerebroventricular injection of streptozotocin (ICV-STZ). We used male adult rats, which were previously treated with an extract rich in ANT (200mg/kg) for seven days. For each study protocol, we used the same dose of ANT only varying the time of drug administration SCO ip (1mg/kg) and ICV-STZ (3mg/kg) specific to the models of amnesia and dementia, respectively. The results showed that pretreatment with ANT reversed the memory deficits in an amnesia model and also in the model of SDAT. Regarding the activity of AChE enzyme was observed a significant increase in SCO group accompanied by a decrease in the activity of Na+, K+-ATPase and Ca2+-ATPase, and these effects were prevented by ANT treatment. It was also observed an increase in NTPDase activity, decreased in ADA and 5'-NT activity from brain of animals injected with SCO, accompanied by a reduction in the ATP and adenosine levels, which can compromise the purinergic signaling. ANT treatment was able to prevent changes in NTPDase, ADA and 5 -NT. The ICV-STZ treated animals showed a high anxiogenic-like behavior and ANT treatment prevented this effect, indicating that it can be seen with anxiolytic properties molecules, as in vitro experiments demonstrated their affinity for the benzodiazepine site of GABAA receptors. The animals ICV-STZ treated showed marked increase in AChE activity and Ca2+-ATPase, and decreased activity of Na+, K+-ATPase, causing disturbances in electrolyte concentrations of Na+ and Ca2+ and this could lead to neuronal excitotoxic and increased activity AChE in SDAT, and these effects were prevented by administration of ANT. Moreover, both the density and immunoreactivity for 5'-NT was markedly reduced in animals ICV-STZ as compared with the group of -normal rats. In addition, ICV-STZ treatment showed a significant decrease in 5'-NT and NTPDase activity in a model of SDAT. In the hippocampus of ICV-STZ animals was found considerable increase in levels of ROS total, MDA and NOx, indicating marked oxidative stress, which could lead to a decrease in neuronal viability and NTPDase and 5'-NT activity, since they are linked to the cell membrane. In this context, we suggest that both cholinergic and purinergic systems can be regulated by ANT treatment, thus defining use of this compound as a new strategy to control the deterioration of memory in aging associated with these systems.
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spelling Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinasStudy of purinergic and cholinergic system and cognitive functions interaction in sporadic dementia of alzheimer type: effects of anthocyaninsAntocianinaMemóriaDemênciaSistema colinergico e purinergicoAnthocyaninMemoryDementiaCholinergic and purinergic systemCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICADementia is a brain disorder characterized by decline in several mental functions and results in deficits in memory functioning in a variety of cognitive tasks. Evidence has emerged showing that anthocyanins (ANT) possess antioxidant, vasodilator and neuroprotective properties, and more recently are able to improve memory. The aim of our study was to investigate the role of ANT on memory and relate these changes to the cholinergic and purinergic in a model of amnesia induced by scopolamine (SCO), in a model of sporadic dementia of the Alzheimer type (SDAT), induced by intracerebroventricular injection of streptozotocin (ICV-STZ). We used male adult rats, which were previously treated with an extract rich in ANT (200mg/kg) for seven days. For each study protocol, we used the same dose of ANT only varying the time of drug administration SCO ip (1mg/kg) and ICV-STZ (3mg/kg) specific to the models of amnesia and dementia, respectively. The results showed that pretreatment with ANT reversed the memory deficits in an amnesia model and also in the model of SDAT. Regarding the activity of AChE enzyme was observed a significant increase in SCO group accompanied by a decrease in the activity of Na+, K+-ATPase and Ca2+-ATPase, and these effects were prevented by ANT treatment. It was also observed an increase in NTPDase activity, decreased in ADA and 5'-NT activity from brain of animals injected with SCO, accompanied by a reduction in the ATP and adenosine levels, which can compromise the purinergic signaling. ANT treatment was able to prevent changes in NTPDase, ADA and 5 -NT. The ICV-STZ treated animals showed a high anxiogenic-like behavior and ANT treatment prevented this effect, indicating that it can be seen with anxiolytic properties molecules, as in vitro experiments demonstrated their affinity for the benzodiazepine site of GABAA receptors. The animals ICV-STZ treated showed marked increase in AChE activity and Ca2+-ATPase, and decreased activity of Na+, K+-ATPase, causing disturbances in electrolyte concentrations of Na+ and Ca2+ and this could lead to neuronal excitotoxic and increased activity AChE in SDAT, and these effects were prevented by administration of ANT. Moreover, both the density and immunoreactivity for 5'-NT was markedly reduced in animals ICV-STZ as compared with the group of -normal rats. In addition, ICV-STZ treatment showed a significant decrease in 5'-NT and NTPDase activity in a model of SDAT. In the hippocampus of ICV-STZ animals was found considerable increase in levels of ROS total, MDA and NOx, indicating marked oxidative stress, which could lead to a decrease in neuronal viability and NTPDase and 5'-NT activity, since they are linked to the cell membrane. In this context, we suggest that both cholinergic and purinergic systems can be regulated by ANT treatment, thus defining use of this compound as a new strategy to control the deterioration of memory in aging associated with these systems.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorA demência é uma desordem cerebral caracterizada por um declínio em várias funções mentais e resulta em déficits no funcionamento da memória e em uma variedade de tarefas cognitivas. Evidências têm surgerido que as antocianinas (ANT) possuem propreidades antioxidantes, vasodilatadoras e neuroprotetoras, sendo capazes de melhorar a memória. O objetivo do nosso trabalho foi investigar o papel das ANT sobre a memória e, relacionar estas mudanças com o sistema colínergico e purinérgico em um modelo de amnésia induzido por escopolamina (SCO), em um modelo de demência esporádica do tipo Alzheimer (DAS), induzido por administração intracerebroventricular de streptozotocina (ICV-STZ). Foram utilizados ratos machos adultos, os quais foram tratados previamente com um extrado rico em ANT (200mg/kg) durante sete dias. Para cada protocolo de estudo, foi utilizada a mesma dose de ANT variando apenas o tempo de administração das drogas SCO ip (1mg/kg) e ICV-STZ (3mg/kg) especificas para aos modelos de amnésia e de demência, respectivamente. Os resultados obtidos demonstraram que o tratamento prévio de ANT reverteu déficits de memória no modelo de amnésia e no modelo de DAS. Em relação à atividade da enzima AChE foi observado um aumento significativo nos grupos SCO acompanhado por uma diminuição da atividade das enzimas Na+,K+-ATPase e Ca2+-ATPase, e estes efeitos foram prevenidos pelo tratamento com ANT. Foi também observado aumento na atividade da NTPDase, diminuição na atividade da ADA e 5 -NT no cérebro de animais injetados com SCO, acompanhado por uma redução nos niveis de ATP e adenosina, ao qual pode comprometer a sinalização purinérgica. E o tratamento com ANT impediu alterações na atividade destas enzimas. Os animais ICV-STZ tratados apresentaram elevado comportamento ansiogênico e o tratamento com ANT previniu este efeito, indicando que as ANT podem ser consideradas moléculas com propriedades ansiolíticas, uma vez que experimentos in vitro, mostraram sua afinidade pelo sítio benzodiazepínico de receptores GABAA. Os animais tratados com ICV-STZ apresentaram marcante elevação na atividade da AChE e Ca2+-ATPase, e redução na atividade da Na+,K+-ATPase, causando perturbações nas concentrações eletrolíticas de Na+ e de Ca2+ e isto poderia levar a excitotoxicidade neuronal e aumento na atividade da AChE na DAS, e estes efeitos foram prevenidos pela administração de ANT. Além disso, tanto a densidade como a immunorreatividade para a 5 -NT foi marcadamente reduzida em animais ICV-STZ em comparação com o grupo de ratos normais. Além disso, o tratamento com STZ mostrou uma diminuição significativa para a atividade da NTPDase e 5 -NT no modelo em animais ICV-STZ tratados. No hipocampo de animais ICV-STZ tratados foi encontrado uma elevação considerável nos níveis de ROS total, MDA e NOx, indicando marcante estresse oxidativo, que poderia levar a diminuição na viabilidade de neurônios e na atividade das enzimas NTPDase e 5 -NT, uma vez que elas estão ligadas a membrana celular. Neste contexto, podemos sugerir que tanto o sistema colinérgico como purinérgico podem ser regulados pelo tratamento com antocianinas, definindo assim, o uso deste composto como uma nova estratégia para controlar a deteriorização mnemônica no envelhecimento associado a esses dos sistemas.Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaSpanevello, Roselia Mariahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4702772A1Barbosa, Nilda Berenice de Vargashttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4795127P7Royes, Luiz Fernando Freirehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849Y0Oliveira, Diogo Losch dehttp://lattes.cnpq.br/3056695127432911Gutierres, Jessié Martins2015-02-042015-02-042013-03-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfGUTIERRES, Jessié Martins. STUDY OF PURINERGIC AND CHOLINERGIC SYSTEM AND COGNITIVE FUNCTIONS INTERACTION IN SPORADIC DEMENTIA OF ALZHEIMER TYPE: EFFECTS OF ANTHOCYANINS. 2013. 212 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2013.http://repositorio.ufsm.br/handle/1/4479ark:/26339/00130000066jvporinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2017-09-12T19:02:10Zoai:repositorio.ufsm.br:1/4479Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-09-12T19:02:10Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas
Study of purinergic and cholinergic system and cognitive functions interaction in sporadic dementia of alzheimer type: effects of anthocyanins
title Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas
spellingShingle Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas
Gutierres, Jessié Martins
Antocianina
Memória
Demência
Sistema colinergico e purinergico
Anthocyanin
Memory
Dementia
Cholinergic and purinergic system
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas
title_full Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas
title_fullStr Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas
title_full_unstemmed Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas
title_sort Estudo da interação do sistema purinérgico, colinérgico e funções cognitivas na demência esporádica do tipo alzheimer: os efeitos das antocianinas
author Gutierres, Jessié Martins
author_facet Gutierres, Jessié Martins
author_role author
dc.contributor.none.fl_str_mv Spanevello, Roselia Maria
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4702772A1
Barbosa, Nilda Berenice de Vargas
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4795127P7
Royes, Luiz Fernando Freire
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705849Y0
Oliveira, Diogo Losch de
http://lattes.cnpq.br/3056695127432911
dc.contributor.author.fl_str_mv Gutierres, Jessié Martins
dc.subject.por.fl_str_mv Antocianina
Memória
Demência
Sistema colinergico e purinergico
Anthocyanin
Memory
Dementia
Cholinergic and purinergic system
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
topic Antocianina
Memória
Demência
Sistema colinergico e purinergico
Anthocyanin
Memory
Dementia
Cholinergic and purinergic system
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Dementia is a brain disorder characterized by decline in several mental functions and results in deficits in memory functioning in a variety of cognitive tasks. Evidence has emerged showing that anthocyanins (ANT) possess antioxidant, vasodilator and neuroprotective properties, and more recently are able to improve memory. The aim of our study was to investigate the role of ANT on memory and relate these changes to the cholinergic and purinergic in a model of amnesia induced by scopolamine (SCO), in a model of sporadic dementia of the Alzheimer type (SDAT), induced by intracerebroventricular injection of streptozotocin (ICV-STZ). We used male adult rats, which were previously treated with an extract rich in ANT (200mg/kg) for seven days. For each study protocol, we used the same dose of ANT only varying the time of drug administration SCO ip (1mg/kg) and ICV-STZ (3mg/kg) specific to the models of amnesia and dementia, respectively. The results showed that pretreatment with ANT reversed the memory deficits in an amnesia model and also in the model of SDAT. Regarding the activity of AChE enzyme was observed a significant increase in SCO group accompanied by a decrease in the activity of Na+, K+-ATPase and Ca2+-ATPase, and these effects were prevented by ANT treatment. It was also observed an increase in NTPDase activity, decreased in ADA and 5'-NT activity from brain of animals injected with SCO, accompanied by a reduction in the ATP and adenosine levels, which can compromise the purinergic signaling. ANT treatment was able to prevent changes in NTPDase, ADA and 5 -NT. The ICV-STZ treated animals showed a high anxiogenic-like behavior and ANT treatment prevented this effect, indicating that it can be seen with anxiolytic properties molecules, as in vitro experiments demonstrated their affinity for the benzodiazepine site of GABAA receptors. The animals ICV-STZ treated showed marked increase in AChE activity and Ca2+-ATPase, and decreased activity of Na+, K+-ATPase, causing disturbances in electrolyte concentrations of Na+ and Ca2+ and this could lead to neuronal excitotoxic and increased activity AChE in SDAT, and these effects were prevented by administration of ANT. Moreover, both the density and immunoreactivity for 5'-NT was markedly reduced in animals ICV-STZ as compared with the group of -normal rats. In addition, ICV-STZ treatment showed a significant decrease in 5'-NT and NTPDase activity in a model of SDAT. In the hippocampus of ICV-STZ animals was found considerable increase in levels of ROS total, MDA and NOx, indicating marked oxidative stress, which could lead to a decrease in neuronal viability and NTPDase and 5'-NT activity, since they are linked to the cell membrane. In this context, we suggest that both cholinergic and purinergic systems can be regulated by ANT treatment, thus defining use of this compound as a new strategy to control the deterioration of memory in aging associated with these systems.
publishDate 2013
dc.date.none.fl_str_mv 2013-03-27
2015-02-04
2015-02-04
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 GUTIERRES, Jessié Martins. STUDY OF PURINERGIC AND CHOLINERGIC SYSTEM AND COGNITIVE FUNCTIONS INTERACTION IN SPORADIC DEMENTIA OF ALZHEIMER TYPE: EFFECTS OF ANTHOCYANINS. 2013. 212 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2013.
http://repositorio.ufsm.br/handle/1/4479
dc.identifier.dark.fl_str_mv ark:/26339/00130000066jv
identifier_str_mv GUTIERRES, Jessié Martins. STUDY OF PURINERGIC AND CHOLINERGIC SYSTEM AND COGNITIVE FUNCTIONS INTERACTION IN SPORADIC DEMENTIA OF ALZHEIMER TYPE: EFFECTS OF ANTHOCYANINS. 2013. 212 f. Tese (Doutorado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2013.
ark:/26339/00130000066jv
url http://repositorio.ufsm.br/handle/1/4479
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
publisher.none.fl_str_mv Universidade Federal de Santa Maria
BR
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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