Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors

Epinephrine (EPI) strengthens contextual fear memories by acting on peripheral β2-adrenoceptors. Phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice are EPI-deficient mice and have reduced contextual fear learning. Our aim was to evaluate the molecular mechanisms by which peripheral EPI s...

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Main Authors: Ana Oliveira, Raquel Martinho, Paula Serrão, Mónica Moreira-Rodrigues
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-09-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnmol.2018.00334/full
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spelling doaj-9808597e496443c683aa33098e89fe912020-11-25T00:18:42ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-09-011110.3389/fnmol.2018.00334396315Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription FactorsAna Oliveira0Ana Oliveira1Raquel Martinho2Raquel Martinho3Paula Serrão4Paula Serrão5Mónica Moreira-Rodrigues6Mónica Moreira-Rodrigues7Laboratory of General Physiology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS/UP), Porto, PortugalCenter for Drug Discovery and Innovative Medicines, University of Porto (MedInUP), Porto, PortugalLaboratory of General Physiology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS/UP), Porto, PortugalCenter for Drug Discovery and Innovative Medicines, University of Porto (MedInUP), Porto, PortugalCenter for Drug Discovery and Innovative Medicines, University of Porto (MedInUP), Porto, PortugalDepartment of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto (FMUP), Porto, PortugalLaboratory of General Physiology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS/UP), Porto, PortugalCenter for Drug Discovery and Innovative Medicines, University of Porto (MedInUP), Porto, PortugalEpinephrine (EPI) strengthens contextual fear memories by acting on peripheral β2-adrenoceptors. Phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice are EPI-deficient mice and have reduced contextual fear learning. Our aim was to evaluate the molecular mechanisms by which peripheral EPI strengthens contextual fear memory and if a β2-adrenoceptor antagonist can erase contextual fear memories. Pnmt-KO and wild-type (WT) mice were submitted to fear conditioning (FC) procedure after treatment with EPI, norepinephrine (NE), EPI plus ICI 118,551 (selective β2-adrenoceptor antagonist), ICI 118,551 or vehicle (NaCl 0.9%). Catecholamines were separated and quantified by high performance liquid chromatography-electrochemical detection (HPLC-ED). Blood glucose was measured by coulometry. Real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression of nuclear receptor 4a1 (Nr4a1), Nr4a2 and Nr4a3 in hippocampus samples. In WT mice, plasma EPI concentration was significantly higher after fear acquisition (FA) compared with mice without the test. NE did not increase in plasma after FA and did not strengthen contextual fear memory, contrary to EPI. Freezing induced by EPI was blocked by ICI 118,551 in Pnmt-KO mice. In WT mice, ICI 118,551 blocked blood glucose release into the bloodstream after FA and decreased contextual fear memory. Nr4a1, Nr4a2 and Nr4a3 mRNA expression decreased in Pnmt-KO mice compared with WT mice after FC procedure. In Pnmt-KO mice, EPI induced an increase in mRNA expression of Nr4a2 compared to vehicle. In conclusion, EPI increases in plasma after an aversive experience, possibly improving long-term and old memories, by acting on peripheral β2-adrenoceptors. Glucose could be the mediator of peripheral EPI in the central nervous system, inducing the expression of Nr4a transcription factor genes involved in consolidation of contextual fear memories.https://www.frontiersin.org/article/10.3389/fnmol.2018.00334/fullepinephrinecontextual fear memorytraumatic experienceβ2-adrenoceptorsNr4a transcription factorsphenylethanolamine-N-methyltransferase-knockout mice
collection DOAJ
language English
format Article
sources DOAJ
author Ana Oliveira
Ana Oliveira
Raquel Martinho
Raquel Martinho
Paula Serrão
Paula Serrão
Mónica Moreira-Rodrigues
Mónica Moreira-Rodrigues
spellingShingle Ana Oliveira
Ana Oliveira
Raquel Martinho
Raquel Martinho
Paula Serrão
Paula Serrão
Mónica Moreira-Rodrigues
Mónica Moreira-Rodrigues
Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors
Frontiers in Molecular Neuroscience
epinephrine
contextual fear memory
traumatic experience
β2-adrenoceptors
Nr4a transcription factors
phenylethanolamine-N-methyltransferase-knockout mice
author_facet Ana Oliveira
Ana Oliveira
Raquel Martinho
Raquel Martinho
Paula Serrão
Paula Serrão
Mónica Moreira-Rodrigues
Mónica Moreira-Rodrigues
author_sort Ana Oliveira
title Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors
title_short Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors
title_full Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors
title_fullStr Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors
title_full_unstemmed Epinephrine Released During Traumatic Events May Strengthen Contextual Fear Memory Through Increased Hippocampus mRNA Expression of Nr4a Transcription Factors
title_sort epinephrine released during traumatic events may strengthen contextual fear memory through increased hippocampus mrna expression of nr4a transcription factors
publisher Frontiers Media S.A.
series Frontiers in Molecular Neuroscience
issn 1662-5099
publishDate 2018-09-01
description Epinephrine (EPI) strengthens contextual fear memories by acting on peripheral β2-adrenoceptors. Phenylethanolamine-N-methyltransferase-knockout (Pnmt-KO) mice are EPI-deficient mice and have reduced contextual fear learning. Our aim was to evaluate the molecular mechanisms by which peripheral EPI strengthens contextual fear memory and if a β2-adrenoceptor antagonist can erase contextual fear memories. Pnmt-KO and wild-type (WT) mice were submitted to fear conditioning (FC) procedure after treatment with EPI, norepinephrine (NE), EPI plus ICI 118,551 (selective β2-adrenoceptor antagonist), ICI 118,551 or vehicle (NaCl 0.9%). Catecholamines were separated and quantified by high performance liquid chromatography-electrochemical detection (HPLC-ED). Blood glucose was measured by coulometry. Real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression of nuclear receptor 4a1 (Nr4a1), Nr4a2 and Nr4a3 in hippocampus samples. In WT mice, plasma EPI concentration was significantly higher after fear acquisition (FA) compared with mice without the test. NE did not increase in plasma after FA and did not strengthen contextual fear memory, contrary to EPI. Freezing induced by EPI was blocked by ICI 118,551 in Pnmt-KO mice. In WT mice, ICI 118,551 blocked blood glucose release into the bloodstream after FA and decreased contextual fear memory. Nr4a1, Nr4a2 and Nr4a3 mRNA expression decreased in Pnmt-KO mice compared with WT mice after FC procedure. In Pnmt-KO mice, EPI induced an increase in mRNA expression of Nr4a2 compared to vehicle. In conclusion, EPI increases in plasma after an aversive experience, possibly improving long-term and old memories, by acting on peripheral β2-adrenoceptors. Glucose could be the mediator of peripheral EPI in the central nervous system, inducing the expression of Nr4a transcription factor genes involved in consolidation of contextual fear memories.
topic epinephrine
contextual fear memory
traumatic experience
β2-adrenoceptors
Nr4a transcription factors
phenylethanolamine-N-methyltransferase-knockout mice
url https://www.frontiersin.org/article/10.3389/fnmol.2018.00334/full
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