Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/49194 https://doi.org/10.3389/fnbeh.2015.00345 |
Resumo: | The effects of flavonoids have been correlated with their ability to modulate the glutamatergic, serotoninergic, and GABAergic neurotransmission: the major targets of these substances are N-methyl-D-aspartic acid receptor (NMDARs), serotonin type1A receptor (5-HT(1A)Rs), and the gamma-aminobutyric acid type A receptors (GABA(A)Rs). Several studies showed that these receptors are involved in the acquisition and extinction of fear memory. This study assessed the effects of treatment prior to conditioning with a flavonoid-rich fraction from the stem bark of Erythrina falcata (FfB) on the acquisition and extinction of the conditioned suppression following pharmacological manipulations and on gene expression in the dorsal hippocampus (DH). Adult male Wistar rats were treated before conditioned fear with FfB, vehicle, an agonist or antagonist of the 5-HT1 AR, GABA(A)Rs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. The effects of these treatments on fear memory retrieval, extinction training and extinction retrieval were evaluated at 48, 72, and 98 h after conditioning, respectively. We found that activation of GABA(A)Rs and inactivation of GluN2B-NMDARs play important roles in the acquisition of lick response suppression. FfB reversed the effect of blocking GluN2B-NMDARs on the conditioned fear and induced the spontaneous recovery. Blocking the 5-HT1AR and the GluN2B-NMDAR before FfB treatment seemed to be associated with weakening of the spontaneous recovery. Expression of analysis of DH samples via qPCR showed that FfB treatment resulted in the overexpression of Htrl a, Grin2a, Gabra5, and Erk2 after the retention test and of Htrl a and Erk2 after the extinction retention test. Moreover, blocking the 5-HT(1A)Rs and the GluN2B-NMDARs before FfB treatment resulted in reduced Htrl a and Grin2b expression after the retention test, but played a distinct role in Grin2a and Erk2 expression, according session evaluated. We show for the first time that the serotoninergic and glutamatergic receptors are important targets for the effect of FfB on the conditioned fear and spontaneous recovery, in which the ERK signaling pathway appears to be modulated. Further, these results provide important information regarding the role of the DH in conditioned suppression. Taken together, our data suggest that FfB represents a potential therapy for preventing or treating memory impairments. |
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Oliveira, Daniela Rodrigues de [UNIFESP]Zamberlam, Claudia Raquel [UNIFESP]Rego, Gizelda MaiaCavalheiro, AlbertoCerutti, Janete Maria [UNIFESP]Cerutti, Suzete Maria [UNIFESP]2019-01-21T10:29:22Z2019-01-21T10:29:22Z2016Frontiers In Behavioral Neuroscience. Lausanne, v. 9, p. 345, 2016.1662-5153http://repositorio.unifesp.br/handle/11600/49194https://doi.org/10.3389/fnbeh.2015.00345WOS000367574300001.pdf10.3389/fnbeh.2015.00345WOS:000367574300001The effects of flavonoids have been correlated with their ability to modulate the glutamatergic, serotoninergic, and GABAergic neurotransmission: the major targets of these substances are N-methyl-D-aspartic acid receptor (NMDARs), serotonin type1A receptor (5-HT(1A)Rs), and the gamma-aminobutyric acid type A receptors (GABA(A)Rs). Several studies showed that these receptors are involved in the acquisition and extinction of fear memory. This study assessed the effects of treatment prior to conditioning with a flavonoid-rich fraction from the stem bark of Erythrina falcata (FfB) on the acquisition and extinction of the conditioned suppression following pharmacological manipulations and on gene expression in the dorsal hippocampus (DH). Adult male Wistar rats were treated before conditioned fear with FfB, vehicle, an agonist or antagonist of the 5-HT1 AR, GABA(A)Rs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. The effects of these treatments on fear memory retrieval, extinction training and extinction retrieval were evaluated at 48, 72, and 98 h after conditioning, respectively. We found that activation of GABA(A)Rs and inactivation of GluN2B-NMDARs play important roles in the acquisition of lick response suppression. FfB reversed the effect of blocking GluN2B-NMDARs on the conditioned fear and induced the spontaneous recovery. Blocking the 5-HT1AR and the GluN2B-NMDAR before FfB treatment seemed to be associated with weakening of the spontaneous recovery. Expression of analysis of DH samples via qPCR showed that FfB treatment resulted in the overexpression of Htrl a, Grin2a, Gabra5, and Erk2 after the retention test and of Htrl a and Erk2 after the extinction retention test. Moreover, blocking the 5-HT(1A)Rs and the GluN2B-NMDARs before FfB treatment resulted in reduced Htrl a and Grin2b expression after the retention test, but played a distinct role in Grin2a and Erk2 expression, according session evaluated. We show for the first time that the serotoninergic and glutamatergic receptors are important targets for the effect of FfB on the conditioned fear and spontaneous recovery, in which the ERK signaling pathway appears to be modulated. Further, these results provide important information regarding the role of the DH in conditioned suppression. Taken together, our data suggest that FfB represents a potential therapy for preventing or treating memory impairments.Sao Paulo State Research Foundation (FAPESP) [2009/15229-3, 2013/20378-8]Cellular and Behavioral Pharmacology Laboratory, Department of Biological Science, Universidade Federal de São Paulo, São Paulo, BrazilGenetic Bases of Thyroid Tumor Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, BrazilDepartment of Forestry Colombo, Brazilian Agricultural Research Corporation, Colombo, BrazilInstitute of Chemistry, Nuclei of Bioassay, Biosynthesis and Ecophysiology of Natural Products, São Paulo State University, Universidade Estadual Paulista, Araraquara, BrazilCellular and Behavioral Pharmacology Laboratory, Department of Biological Science, Universidade Federal de São Paulo, Diadema, BrazilGenetic Bases of Thyroid Tumor Laboratory, Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, BrazilFAPESP: 2009/15229-3FAPESP: 2013/20378-8Web of Science345engUniversidade De FortalezaFrontiers In Behavioral NeuroscienceFlavonesFear MemoryGaba(A)R5-Ht1arGlun2b-NmdarConditioned Emotional ResponseLong-Term PotentiationMethyl-D-AspartateVentromedial Prefrontal CortexActivated Protein-KinaseGamma-Aminobutyric-AcidGinkgo-Biloba ExtractGaba(A) ReceptorNmda Receptors5-Ht1a ReceptorsEffects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approachesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000367574300001.pdfapplication/pdf7359117${dspace.ui.url}/bitstream/11600/49194/1/WOS000367574300001.pdf85c058f9e2f846be81d88233fc7ec37dMD51open accessTEXTWOS000367574300001.pdf.txtWOS000367574300001.pdf.txtExtracted texttext/plain119085${dspace.ui.url}/bitstream/11600/49194/8/WOS000367574300001.pdf.txtd6e424800bfdea861563738875cf7125MD58open accessTHUMBNAILWOS000367574300001.pdf.jpgWOS000367574300001.pdf.jpgIM Thumbnailimage/jpeg6727${dspace.ui.url}/bitstream/11600/49194/10/WOS000367574300001.pdf.jpg543bd6c4ef7397c758645038587f8b7dMD510open access11600/491942023-06-05 19:31:04.256open accessoai:repositorio.unifesp.br:11600/49194Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:31:04Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches |
title |
Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches |
spellingShingle |
Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches Oliveira, Daniela Rodrigues de [UNIFESP] Flavones Fear Memory Gaba(A)R 5-Ht1ar Glun2b-NmdarConditioned Emotional Response Long-Term Potentiation Methyl-D-Aspartate Ventromedial Prefrontal Cortex Activated Protein-Kinase Gamma-Aminobutyric-Acid Ginkgo-Biloba Extract Gaba(A) Receptor Nmda Receptors 5-Ht1a Receptors |
title_short |
Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches |
title_full |
Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches |
title_fullStr |
Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches |
title_full_unstemmed |
Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches |
title_sort |
Effects of a flavonoid-rich fraction on the acquisition and extinction of fear memory: pharmacological and molecular approaches |
author |
Oliveira, Daniela Rodrigues de [UNIFESP] |
author_facet |
Oliveira, Daniela Rodrigues de [UNIFESP] Zamberlam, Claudia Raquel [UNIFESP] Rego, Gizelda Maia Cavalheiro, Alberto Cerutti, Janete Maria [UNIFESP] Cerutti, Suzete Maria [UNIFESP] |
author_role |
author |
author2 |
Zamberlam, Claudia Raquel [UNIFESP] Rego, Gizelda Maia Cavalheiro, Alberto Cerutti, Janete Maria [UNIFESP] Cerutti, Suzete Maria [UNIFESP] |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Oliveira, Daniela Rodrigues de [UNIFESP] Zamberlam, Claudia Raquel [UNIFESP] Rego, Gizelda Maia Cavalheiro, Alberto Cerutti, Janete Maria [UNIFESP] Cerutti, Suzete Maria [UNIFESP] |
dc.subject.eng.fl_str_mv |
Flavones Fear Memory Gaba(A)R 5-Ht1ar Glun2b-NmdarConditioned Emotional Response Long-Term Potentiation Methyl-D-Aspartate Ventromedial Prefrontal Cortex Activated Protein-Kinase Gamma-Aminobutyric-Acid Ginkgo-Biloba Extract Gaba(A) Receptor Nmda Receptors 5-Ht1a Receptors |
topic |
Flavones Fear Memory Gaba(A)R 5-Ht1ar Glun2b-NmdarConditioned Emotional Response Long-Term Potentiation Methyl-D-Aspartate Ventromedial Prefrontal Cortex Activated Protein-Kinase Gamma-Aminobutyric-Acid Ginkgo-Biloba Extract Gaba(A) Receptor Nmda Receptors 5-Ht1a Receptors |
description |
The effects of flavonoids have been correlated with their ability to modulate the glutamatergic, serotoninergic, and GABAergic neurotransmission: the major targets of these substances are N-methyl-D-aspartic acid receptor (NMDARs), serotonin type1A receptor (5-HT(1A)Rs), and the gamma-aminobutyric acid type A receptors (GABA(A)Rs). Several studies showed that these receptors are involved in the acquisition and extinction of fear memory. This study assessed the effects of treatment prior to conditioning with a flavonoid-rich fraction from the stem bark of Erythrina falcata (FfB) on the acquisition and extinction of the conditioned suppression following pharmacological manipulations and on gene expression in the dorsal hippocampus (DH). Adult male Wistar rats were treated before conditioned fear with FfB, vehicle, an agonist or antagonist of the 5-HT1 AR, GABA(A)Rs or the GluN2B-NMDAR or one of these antagonists before FfB treatment. The effects of these treatments on fear memory retrieval, extinction training and extinction retrieval were evaluated at 48, 72, and 98 h after conditioning, respectively. We found that activation of GABA(A)Rs and inactivation of GluN2B-NMDARs play important roles in the acquisition of lick response suppression. FfB reversed the effect of blocking GluN2B-NMDARs on the conditioned fear and induced the spontaneous recovery. Blocking the 5-HT1AR and the GluN2B-NMDAR before FfB treatment seemed to be associated with weakening of the spontaneous recovery. Expression of analysis of DH samples via qPCR showed that FfB treatment resulted in the overexpression of Htrl a, Grin2a, Gabra5, and Erk2 after the retention test and of Htrl a and Erk2 after the extinction retention test. Moreover, blocking the 5-HT(1A)Rs and the GluN2B-NMDARs before FfB treatment resulted in reduced Htrl a and Grin2b expression after the retention test, but played a distinct role in Grin2a and Erk2 expression, according session evaluated. We show for the first time that the serotoninergic and glutamatergic receptors are important targets for the effect of FfB on the conditioned fear and spontaneous recovery, in which the ERK signaling pathway appears to be modulated. Further, these results provide important information regarding the role of the DH in conditioned suppression. Taken together, our data suggest that FfB represents a potential therapy for preventing or treating memory impairments. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2019-01-21T10:29:22Z |
dc.date.available.fl_str_mv |
2019-01-21T10:29:22Z |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Frontiers In Behavioral Neuroscience. Lausanne, v. 9, p. 345, 2016. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/49194 https://doi.org/10.3389/fnbeh.2015.00345 |
dc.identifier.issn.none.fl_str_mv |
1662-5153 |
dc.identifier.file.none.fl_str_mv |
WOS000367574300001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.3389/fnbeh.2015.00345 |
dc.identifier.wos.none.fl_str_mv |
WOS:000367574300001 |
identifier_str_mv |
Frontiers In Behavioral Neuroscience. Lausanne, v. 9, p. 345, 2016. 1662-5153 WOS000367574300001.pdf 10.3389/fnbeh.2015.00345 WOS:000367574300001 |
url |
http://repositorio.unifesp.br/handle/11600/49194 https://doi.org/10.3389/fnbeh.2015.00345 |
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eng |
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eng |
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Frontiers In Behavioral Neuroscience |
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openAccess |
dc.format.none.fl_str_mv |
345 |
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Universidade De Fortaleza |
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Universidade De Fortaleza |
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Repositório Institucional da UNIFESP |
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