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Intrinsic Up-Regulation of 2-AG Favors an Area Specific Neuronal Survival in Different In Vitro Models of Neuronal Damage

BACKGROUND: The endocannabinoid 2-arachidonoyl glycerol (2-AG) acts as a retrograde messenger and modulates synaptic signaling e. g. in the hippocampus. 2-AG also exerts neuroprotective effects under pathological situations. To better understand the mechanism beyond physiological signaling we used O...

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Autores principales: Kallendrusch, Sonja, Hobusch, Constance, Ehrlich, Angela, Nowicki, Marcin, Ziebell, Simone, Bechmann, Ingo, Geisslinger, Gerd, Koch, Marco, Dehghani, Faramarz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527460/
https://www.ncbi.nlm.nih.gov/pubmed/23284665
http://dx.doi.org/10.1371/journal.pone.0051208
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author Kallendrusch, Sonja
Hobusch, Constance
Ehrlich, Angela
Nowicki, Marcin
Ziebell, Simone
Bechmann, Ingo
Geisslinger, Gerd
Koch, Marco
Dehghani, Faramarz
author_facet Kallendrusch, Sonja
Hobusch, Constance
Ehrlich, Angela
Nowicki, Marcin
Ziebell, Simone
Bechmann, Ingo
Geisslinger, Gerd
Koch, Marco
Dehghani, Faramarz
author_sort Kallendrusch, Sonja
collection PubMed
description BACKGROUND: The endocannabinoid 2-arachidonoyl glycerol (2-AG) acts as a retrograde messenger and modulates synaptic signaling e. g. in the hippocampus. 2-AG also exerts neuroprotective effects under pathological situations. To better understand the mechanism beyond physiological signaling we used Organotypic Entorhino-Hippocampal Slice Cultures (OHSC) and investigated the temporal regulation of 2-AG in different cell subsets during excitotoxic lesion and dendritic lesion of long range projections in the enthorhinal cortex (EC), dentate gyrus (DG) and the cornu ammonis region 1 (CA1). RESULTS: 2-AG levels were elevated 24 h after excitotoxic lesion in CA1 and DG (but not EC) and 24 h after perforant pathway transection (PPT) in the DG only. After PPT diacylglycerol lipase alpha (DAGL) protein, the synthesizing enzyme of 2-AG was decreased when Dagl mRNA expression and 2-AG levels were enhanced. In contrast to DAGL, the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MAGL) showed no alterations in total protein and mRNA expression after PPT in OHSC. MAGL immunoreaction underwent a redistribution after PPT and excitotoxic lesion since MAGL IR disappeared in astrocytes of lesioned OHSC. DAGL and MAGL immunoreactions were not detectable in microglia at all investigated time points. Thus, induction of the neuroprotective endocannabinoid 2-AG might be generally accomplished by down-regulation of MAGL in astrocytes after neuronal lesions. CONCLUSION: Increase in 2-AG levels during secondary neuronal damage reflects a general neuroprotective mechanism since it occurred independently in both different lesion models. This intrinsic up-regulation of 2-AG is synergistically controlled by DAGL and MAGL in neurons and astrocytes and thus represents a protective system for neurons that is involved in dendritic reorganisation.
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spelling pubmed-35274602013-01-02 Intrinsic Up-Regulation of 2-AG Favors an Area Specific Neuronal Survival in Different In Vitro Models of Neuronal Damage Kallendrusch, Sonja Hobusch, Constance Ehrlich, Angela Nowicki, Marcin Ziebell, Simone Bechmann, Ingo Geisslinger, Gerd Koch, Marco Dehghani, Faramarz PLoS One Research Article BACKGROUND: The endocannabinoid 2-arachidonoyl glycerol (2-AG) acts as a retrograde messenger and modulates synaptic signaling e. g. in the hippocampus. 2-AG also exerts neuroprotective effects under pathological situations. To better understand the mechanism beyond physiological signaling we used Organotypic Entorhino-Hippocampal Slice Cultures (OHSC) and investigated the temporal regulation of 2-AG in different cell subsets during excitotoxic lesion and dendritic lesion of long range projections in the enthorhinal cortex (EC), dentate gyrus (DG) and the cornu ammonis region 1 (CA1). RESULTS: 2-AG levels were elevated 24 h after excitotoxic lesion in CA1 and DG (but not EC) and 24 h after perforant pathway transection (PPT) in the DG only. After PPT diacylglycerol lipase alpha (DAGL) protein, the synthesizing enzyme of 2-AG was decreased when Dagl mRNA expression and 2-AG levels were enhanced. In contrast to DAGL, the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MAGL) showed no alterations in total protein and mRNA expression after PPT in OHSC. MAGL immunoreaction underwent a redistribution after PPT and excitotoxic lesion since MAGL IR disappeared in astrocytes of lesioned OHSC. DAGL and MAGL immunoreactions were not detectable in microglia at all investigated time points. Thus, induction of the neuroprotective endocannabinoid 2-AG might be generally accomplished by down-regulation of MAGL in astrocytes after neuronal lesions. CONCLUSION: Increase in 2-AG levels during secondary neuronal damage reflects a general neuroprotective mechanism since it occurred independently in both different lesion models. This intrinsic up-regulation of 2-AG is synergistically controlled by DAGL and MAGL in neurons and astrocytes and thus represents a protective system for neurons that is involved in dendritic reorganisation. Public Library of Science 2012-12-20 /pmc/articles/PMC3527460/ /pubmed/23284665 http://dx.doi.org/10.1371/journal.pone.0051208 Text en © 2012 Kallendrusch et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kallendrusch, Sonja
Hobusch, Constance
Ehrlich, Angela
Nowicki, Marcin
Ziebell, Simone
Bechmann, Ingo
Geisslinger, Gerd
Koch, Marco
Dehghani, Faramarz
Intrinsic Up-Regulation of 2-AG Favors an Area Specific Neuronal Survival in Different In Vitro Models of Neuronal Damage
title Intrinsic Up-Regulation of 2-AG Favors an Area Specific Neuronal Survival in Different In Vitro Models of Neuronal Damage
title_full Intrinsic Up-Regulation of 2-AG Favors an Area Specific Neuronal Survival in Different In Vitro Models of Neuronal Damage
title_fullStr Intrinsic Up-Regulation of 2-AG Favors an Area Specific Neuronal Survival in Different In Vitro Models of Neuronal Damage
title_full_unstemmed Intrinsic Up-Regulation of 2-AG Favors an Area Specific Neuronal Survival in Different In Vitro Models of Neuronal Damage
title_short Intrinsic Up-Regulation of 2-AG Favors an Area Specific Neuronal Survival in Different In Vitro Models of Neuronal Damage
title_sort intrinsic up-regulation of 2-ag favors an area specific neuronal survival in different in vitro models of neuronal damage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527460/
https://www.ncbi.nlm.nih.gov/pubmed/23284665
http://dx.doi.org/10.1371/journal.pone.0051208
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