Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/3864 |
Resumo: | Fatty acids (FA) are constituents of neuronal phospholipid membranes, where they are essential for the development and functioning of the brain. During the peak of neuronal growth, occurring during the last week of gestation and lactation, there is a rapid accumulation of long-chain polyunsaturated FA (LC-PUFAs), which are synthesized from a physiologically appropriate supply of essential fatty acids (EFA) for normal fetal and neonatal development , ensuring the development of neurological functions. During the last decades, there occurred changes in dietary habits in Western countries, mainly with increased consumption of trans fatty acids (TFA) and omega-6 (n-6) at the expense of consumption of omega-3 (n-3). These changes may increase oxidative damage and alter neuronal neuroplasticity, thereby facilitating the development of neuropsychiatric diseases such as bipolar disorder (BD). Through a model of amphetamine-induced mania in rats, we evaluated comparatively the influence of daily supplementation of different fats since pre-conception until weaning of 1st and 2nd generation litters on behavioral parameters in conjunction with biochemical changes in brain regions. Three groups of female Wistar rats were supplemented (3g/kg; p.o. per day) from one week before conception through pregnancy and breast-feeding with fish oil (FO, rich in n-3 PUFA), soybean oil (SO; rich in PUFA n-6) or hydrogenated vegetable fat (HVF; rich in TFA). During weaning, pups of both sexes were kept under the original supplementation until 90 days of age. While male offspring were included in the study of the 1st generation, females were mated and maintained in the same supplementation, thus obtaining animals of the 2nd generation, which were used in the 2nd study and divided into 3 experiments. In the study of the 1st generation at 90 days of age, one half of each supplementation group was treated with a daily dose of amphetamine (AMPH 4mg/kg, ip) or saline (control) for 14 days, when they were subjected to behavioral tests and biochemical assessments in the cortex, striatum and hippocampus. HVF supplementation was associated with TFA incorporation in the three structures, increased AMPH-induced locomotor activity, and increased oxidative damage. Since FO supplementation increased DHA percentage and decreased the n6/n3 ratio in the three regions analyzed, it may have improved membrane fluidity and reduced oxidative stress in such animals. Adult male rats born from the 2nd generation were also exposed to an animal model of mania induced by amphetamine and used in two different experiments. In the first experiment, animals were evaluated for memory behavior and biochemical and molecular analysis in the hippocampus, in which these parameters were decreased by HVF supplementation and improved by FO supplementation. In the second experiment, animals were evaluated regarding hyperactivity and biochemical and molecular analyses in the cortex, where again HVF supplementation was associated with loss in some parameters. In a third experiment we evaluated the influence of trans fat supplementation in rats exposed to the same mania animal model and the response to lithium (a mood stabilizing drug) treatment in 1st and 2nd generation animals. Lithium was able to reverse all AMPH-induced effects. Taken together, our findings suggest that the increased consumption of processed foods, which are rich in trans fat, may be related to an increased incidence of neuropsychiatric conditions. Conversely, a balanced diet, which includes omega-3 sources , reduces susceptibility to developing such conditions, possibly by changing the composition of the neuronal phospholipid membrane. |
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Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de maniaEffects of the consumption of n-3, n-6 and trans fatty acids on biochemical and molecular aspects in an animal model of maniaAGPI n-3 e n-6Gordura transEstresse oxidativoNeuroplasticidadeTranstorno bipolarPUFAs n-3 and n-6Trans fatOxidative stressNeuroplasticityBipolar disorderCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAFatty acids (FA) are constituents of neuronal phospholipid membranes, where they are essential for the development and functioning of the brain. During the peak of neuronal growth, occurring during the last week of gestation and lactation, there is a rapid accumulation of long-chain polyunsaturated FA (LC-PUFAs), which are synthesized from a physiologically appropriate supply of essential fatty acids (EFA) for normal fetal and neonatal development , ensuring the development of neurological functions. During the last decades, there occurred changes in dietary habits in Western countries, mainly with increased consumption of trans fatty acids (TFA) and omega-6 (n-6) at the expense of consumption of omega-3 (n-3). These changes may increase oxidative damage and alter neuronal neuroplasticity, thereby facilitating the development of neuropsychiatric diseases such as bipolar disorder (BD). Through a model of amphetamine-induced mania in rats, we evaluated comparatively the influence of daily supplementation of different fats since pre-conception until weaning of 1st and 2nd generation litters on behavioral parameters in conjunction with biochemical changes in brain regions. Three groups of female Wistar rats were supplemented (3g/kg; p.o. per day) from one week before conception through pregnancy and breast-feeding with fish oil (FO, rich in n-3 PUFA), soybean oil (SO; rich in PUFA n-6) or hydrogenated vegetable fat (HVF; rich in TFA). During weaning, pups of both sexes were kept under the original supplementation until 90 days of age. While male offspring were included in the study of the 1st generation, females were mated and maintained in the same supplementation, thus obtaining animals of the 2nd generation, which were used in the 2nd study and divided into 3 experiments. In the study of the 1st generation at 90 days of age, one half of each supplementation group was treated with a daily dose of amphetamine (AMPH 4mg/kg, ip) or saline (control) for 14 days, when they were subjected to behavioral tests and biochemical assessments in the cortex, striatum and hippocampus. HVF supplementation was associated with TFA incorporation in the three structures, increased AMPH-induced locomotor activity, and increased oxidative damage. Since FO supplementation increased DHA percentage and decreased the n6/n3 ratio in the three regions analyzed, it may have improved membrane fluidity and reduced oxidative stress in such animals. Adult male rats born from the 2nd generation were also exposed to an animal model of mania induced by amphetamine and used in two different experiments. In the first experiment, animals were evaluated for memory behavior and biochemical and molecular analysis in the hippocampus, in which these parameters were decreased by HVF supplementation and improved by FO supplementation. In the second experiment, animals were evaluated regarding hyperactivity and biochemical and molecular analyses in the cortex, where again HVF supplementation was associated with loss in some parameters. In a third experiment we evaluated the influence of trans fat supplementation in rats exposed to the same mania animal model and the response to lithium (a mood stabilizing drug) treatment in 1st and 2nd generation animals. Lithium was able to reverse all AMPH-induced effects. Taken together, our findings suggest that the increased consumption of processed foods, which are rich in trans fat, may be related to an increased incidence of neuropsychiatric conditions. Conversely, a balanced diet, which includes omega-3 sources , reduces susceptibility to developing such conditions, possibly by changing the composition of the neuronal phospholipid membrane.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorÁcidos graxos (AG) são fosfolipídeos constituintes das membranas neuronais onde são fundamentais para o desenvolvimento e funcionamento do cérebro. Durante o pico do crescimento neuronal, o qual ocorre durante a última semana de gestação e período de aleitamento, há um rápido acúmulo de AG poliinsaturados de cadeia longa (AGPI-CL) para o desenvolvimento fetal e neonatal normal, garantindo o desenvolvimento de suas funções neurológicas. Durante as últimas décadas foram observadas mudanças nos hábitos alimentares, principalmente em países ocidentais, devido ao aumento do consumo de AG trans e ômega-6 (n-6) em detrimento do consumo de AG ômega-3 (n-3). Estas mudanças podem favorecer o desenvolvimento de processos oxidativos e alterar a neuroplasticidade neuronal, facilitando assim o desenvolvimento de doenças neuropsiquiátricas, e dentre estas, o transtorno bipolar (TB). Através de um modelo animal de mania induzido por anfetamina, avaliamos comparativamente a influência da suplementação diária de óleos ou gordura desde o período pré-concepcional até o desmame das ninhadas em regiões cerebrais dos filhotes de 1ª e de 2ª geração. Três grupos de ratas Wistar foram suplementadas diariamente (3g/kg/v.o.) desde uma semana antes da concepção, durante a gestação e aleitamento com óleo de peixe (OP, rico em AGPI n-3); óleo de soja (rico em AGPI n-6) ou gordura vegetal hidrogenada (GVH; rica em AGT). No período de desmame, filhotes de ambos os sexos foram mantidos sob a mesma suplementação original até 90 dias de idade. Enquanto os filhotes machos foram incluídos no estudo da 1ª geração, as fêmeas foram separadas e acasaladas nas mesmas condições de suplementação já descritas, obtendo-se assim, animais adultos de 2ª geração, os quais foram incluídos no 2º estudo e divididos em 3 experimentos. No estudo de 1ª geração, aos 90 dias de idade, metade de cada suplementação foi tratada com uma dose diária de anfetamina (4mg/Kg, ip) ou solução salina (controle), durante 14 dias, quando foram submetidos aos testes comportamentais e avaliações bioquímicas no córtex, estriado e hipocampo. A suplementação com GVH favoreceu a incorporação de AGT nas três estruturas cerebrais descritas, aumentou a atividade locomotora induzida por ANF e aumentou os danos oxidativos. Já a suplementação com OP permitiu um aumento da porcentagem de DHA, diminuindo a razão AGPI n6/n3 nas três regiões avaliadas, o que pode ter contribuído para uma maior fluidez das membranas neurais e menor incidência de danos oxidativos. Ratos machos adultos da 2ª geração foram também expostos ao modelo animal de mania induzido por anfetamina, sendo porém separados em dois experimentos distintos: no primeiro experimento, além de avaliações comportamentais relacionadas à memória, marcadores do status oxidativo e análises moleculares foram feitas no hipocampo, sendo observado um prejuízo destes parâmetros no grupo suplementado com GVH, enquanto o grupo OP mostrou efeitos benéficos. No segundo experimento, além do comportamento locomotor, análises bioquímicas e moleculares foram feitas no córtex, quando novamente, a suplementação com GVH mostrou efeitos deletérios. No terceiro experimento avaliamos a influência da suplementação de gordura trans em animais de 1ª e 2ª geração sobre o mesmo modelo animal de mania e a resposta farmacológica ao carbonato de lítio (droga estabilizadora do humor), quando observamos que o lítio foi capaz de reverter todos efeitos induzidos pela ANF. Tomados em conjunto, os dados apresentados nesta tese sugerem que o consumo aumentado de alimentos industrializados, os quais são ricos em grodura trans, podem estar envolvidos no aumento da incidência de doenças neuropsiquiátricas. Contrariamente, uma alimentação balanceada, a qual inclui fontes de omega-3, reduz a suscetibilidade para o desenvolvimento de tais condições, em decorrência das possíveis alterações na composição fosfolipídica das membranas neurais.Universidade Federal de Santa MariaBRFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaBurger, Marilise Escobarhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6Mello, Carlos Fernando dehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782674D2Oliveira, Mauro Schneiderhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705848A9Fachinetto, Roseleihttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2Emanuelli, Tatianahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797080Z5Trevizol, Fabíola2016-12-192016-12-192014-07-18info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfTREVIZOL, Fabíola. EFFECTS OF THE CONSUMPTION OF N-3, N-6 AND TRANS FATTY ACIDS ON BIOCHEMICAL AND MOLECULAR ASPECTS IN AN ANIMAL MODEL OF MANIA. 2014. 190 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014.http://repositorio.ufsm.br/handle/1/3864porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2017-09-11T18:11:57Zoai:repositorio.ufsm.br:1/3864Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-09-11T18:11:57Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania Effects of the consumption of n-3, n-6 and trans fatty acids on biochemical and molecular aspects in an animal model of mania |
title |
Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania |
spellingShingle |
Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania Trevizol, Fabíola AGPI n-3 e n-6 Gordura trans Estresse oxidativo Neuroplasticidade Transtorno bipolar PUFAs n-3 and n-6 Trans fat Oxidative stress Neuroplasticity Bipolar disorder CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania |
title_full |
Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania |
title_fullStr |
Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania |
title_full_unstemmed |
Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania |
title_sort |
Efeitos do consumo de ácidos graxos n-3, n-6 e trans sobre aspectos bioquímicos e moleculares em um modelo animal de mania |
author |
Trevizol, Fabíola |
author_facet |
Trevizol, Fabíola |
author_role |
author |
dc.contributor.none.fl_str_mv |
Burger, Marilise Escobar http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6 Mello, Carlos Fernando de http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782674D2 Oliveira, Mauro Schneider http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705848A9 Fachinetto, Roselei http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4755373E2 Emanuelli, Tatiana http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797080Z5 |
dc.contributor.author.fl_str_mv |
Trevizol, Fabíola |
dc.subject.por.fl_str_mv |
AGPI n-3 e n-6 Gordura trans Estresse oxidativo Neuroplasticidade Transtorno bipolar PUFAs n-3 and n-6 Trans fat Oxidative stress Neuroplasticity Bipolar disorder CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
AGPI n-3 e n-6 Gordura trans Estresse oxidativo Neuroplasticidade Transtorno bipolar PUFAs n-3 and n-6 Trans fat Oxidative stress Neuroplasticity Bipolar disorder CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Fatty acids (FA) are constituents of neuronal phospholipid membranes, where they are essential for the development and functioning of the brain. During the peak of neuronal growth, occurring during the last week of gestation and lactation, there is a rapid accumulation of long-chain polyunsaturated FA (LC-PUFAs), which are synthesized from a physiologically appropriate supply of essential fatty acids (EFA) for normal fetal and neonatal development , ensuring the development of neurological functions. During the last decades, there occurred changes in dietary habits in Western countries, mainly with increased consumption of trans fatty acids (TFA) and omega-6 (n-6) at the expense of consumption of omega-3 (n-3). These changes may increase oxidative damage and alter neuronal neuroplasticity, thereby facilitating the development of neuropsychiatric diseases such as bipolar disorder (BD). Through a model of amphetamine-induced mania in rats, we evaluated comparatively the influence of daily supplementation of different fats since pre-conception until weaning of 1st and 2nd generation litters on behavioral parameters in conjunction with biochemical changes in brain regions. Three groups of female Wistar rats were supplemented (3g/kg; p.o. per day) from one week before conception through pregnancy and breast-feeding with fish oil (FO, rich in n-3 PUFA), soybean oil (SO; rich in PUFA n-6) or hydrogenated vegetable fat (HVF; rich in TFA). During weaning, pups of both sexes were kept under the original supplementation until 90 days of age. While male offspring were included in the study of the 1st generation, females were mated and maintained in the same supplementation, thus obtaining animals of the 2nd generation, which were used in the 2nd study and divided into 3 experiments. In the study of the 1st generation at 90 days of age, one half of each supplementation group was treated with a daily dose of amphetamine (AMPH 4mg/kg, ip) or saline (control) for 14 days, when they were subjected to behavioral tests and biochemical assessments in the cortex, striatum and hippocampus. HVF supplementation was associated with TFA incorporation in the three structures, increased AMPH-induced locomotor activity, and increased oxidative damage. Since FO supplementation increased DHA percentage and decreased the n6/n3 ratio in the three regions analyzed, it may have improved membrane fluidity and reduced oxidative stress in such animals. Adult male rats born from the 2nd generation were also exposed to an animal model of mania induced by amphetamine and used in two different experiments. In the first experiment, animals were evaluated for memory behavior and biochemical and molecular analysis in the hippocampus, in which these parameters were decreased by HVF supplementation and improved by FO supplementation. In the second experiment, animals were evaluated regarding hyperactivity and biochemical and molecular analyses in the cortex, where again HVF supplementation was associated with loss in some parameters. In a third experiment we evaluated the influence of trans fat supplementation in rats exposed to the same mania animal model and the response to lithium (a mood stabilizing drug) treatment in 1st and 2nd generation animals. Lithium was able to reverse all AMPH-induced effects. Taken together, our findings suggest that the increased consumption of processed foods, which are rich in trans fat, may be related to an increased incidence of neuropsychiatric conditions. Conversely, a balanced diet, which includes omega-3 sources , reduces susceptibility to developing such conditions, possibly by changing the composition of the neuronal phospholipid membrane. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-07-18 2016-12-19 2016-12-19 |
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 |
TREVIZOL, Fabíola. EFFECTS OF THE CONSUMPTION OF N-3, N-6 AND TRANS FATTY ACIDS ON BIOCHEMICAL AND MOLECULAR ASPECTS IN AN ANIMAL MODEL OF MANIA. 2014. 190 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014. http://repositorio.ufsm.br/handle/1/3864 |
identifier_str_mv |
TREVIZOL, Fabíola. EFFECTS OF THE CONSUMPTION OF N-3, N-6 AND TRANS FATTY ACIDS ON BIOCHEMICAL AND MOLECULAR ASPECTS IN AN ANIMAL MODEL OF MANIA. 2014. 190 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
url |
http://repositorio.ufsm.br/handle/1/3864 |
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 Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
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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1805922140539584512 |