Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.

Pérez Martín, Ester; Pérez Revuelta, Laura; Barahona López, Cristina; Pérez Boyero, David; Alonso Peña, José Ramón; Díaz López, David; Weruaga Prieto, Eduardo

Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.

[EN] Neurodegenerative diseases involve an exacerbated neuroinflammatory response led by microglia that triggers cytokine storm and leukocyte infiltration into the brain. PPARα agonists partially dampen this neuroinflammation in some models of brain insult, but neuronal loss was not the triggering c...

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Autores:	Pérez Martín, Ester, Pérez Revuelta, Laura, Barahona López, Cristina, Pérez Boyero, David, Alonso Peña, José Ramón, Díaz López, David, Weruaga Prieto, Eduardo
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2023
País:	España
Institución:	Universidad de Salamanca (USAL)
Repositorio:	GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:	oai:gredos.usal.es:10366/168676
Acceso en línea:	http://hdl.handle.net/10366/168676
Access Level:	acceso abierto
Palabra clave:	Endocannabinoids Microglia Neurodegeneration Neuroinflammation Neurotherapeutics Oleoylethanolamide (OEA) PCD mouse Purkinje cells Oleic Acids Animals PPAR alpha Cerebellum Anti-Inflammatory Agents Mice 2490 Neurociencias 2412 Inmunología cerebelo ácidos oleicos PPAR alfa animales ratones endocannabinoides antiinflamatorios

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spelling	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.Pérez Martín, EsterPérez Revuelta, LauraBarahona López, CristinaPérez Boyero, DavidAlonso Peña, José RamónDíaz López, DavidWeruaga Prieto, EduardoEndocannabinoidsMicrogliaNeurodegenerationNeuroinflammationNeurotherapeuticsOleoylethanolamide (OEA)PCD mousePurkinje cellsOleic AcidsAnimalsPPAR alphaCerebellumEndocannabinoidsAnti-Inflammatory AgentsMice2490 Neurociencias2412 Inmunologíacerebeloácidos oleicosPPAR alfaanimalesratonesendocannabinoidesantiinflamatorios[EN] Neurodegenerative diseases involve an exacerbated neuroinflammatory response led by microglia that triggers cytokine storm and leukocyte infiltration into the brain. PPARα agonists partially dampen this neuroinflammation in some models of brain insult, but neuronal loss was not the triggering cause in any of them. This study examines the anti-inflammatory and immunomodulatory properties of the PPARα agonist oleoylethanolamide (OEA) in the Purkinje Cell Degeneration (PCD) mouse, which exhibits striking neuroinflammation caused by aggressive loss of cerebellar Purkinje neurons. Using real-time quantitative polymerase chain reaction and immunostaining, we quantified changes in pro- and anti-inflammatory markers, microglial density and marker-based phenotype, and overall leukocyte recruitment at different time points after OEA administration. OEA was found to modulate cerebellar neuroinflammation by increasing the gene expression of proinflammatory mediators at the onset of neurodegeneration and decreasing it over time. OEA also enhanced the expression of anti-inflammatory and neuroprotective factors and the Pparα gene. Regarding microgliosis, OEA reduced microglial density-especially in regions where it is preferentially located in PCD mice-and shifted the microglial phenotype towards an anti-inflammatory state. Finally, OEA prevented massive leukocyte infiltration into the cerebellum. Overall, our findings suggest that OEA may change the environment to protect neurons from degeneration caused by exacerbated inflammation.This work was supported by the Spanish Ministry of Science and Innovation (PID2019- 106943RB-I00 to E.W.), the Ministry of Science and Innovation/Universities (FPU16/04259 to E.P.-M.), the Regional Government of Castile and Leon (SA129P20 to E.W.; EDU/556/2019 to L.P.-R.), the Centre for Regenerative Medicine and Cell Therapy of Castile and Leon (E.W.), and the University of Salamanca.MDPI202620262023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplicatio/pdfhttp://hdl.handle.net/10366/168676reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésFPU16/04259PID2019- 106943RB-I00SA129P20EDU/556/2019Attribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1686762026-06-07T06:28:51Z
dc.title.none.fl_str_mv	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.
title	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.
spellingShingle	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration. Pérez Martín, Ester Endocannabinoids Microglia Neurodegeneration Neuroinflammation Neurotherapeutics Oleoylethanolamide (OEA) PCD mouse Purkinje cells Oleic Acids Animals PPAR alpha Cerebellum Endocannabinoids Anti-Inflammatory Agents Mice 2490 Neurociencias 2412 Inmunología cerebelo ácidos oleicos PPAR alfa animales ratones endocannabinoides antiinflamatorios
title_short	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.
title_full	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.
title_fullStr	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.
title_full_unstemmed	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.
title_sort	Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.
dc.creator.none.fl_str_mv	Pérez Martín, Ester Pérez Revuelta, Laura Barahona López, Cristina Pérez Boyero, David Alonso Peña, José Ramón Díaz López, David Weruaga Prieto, Eduardo
author	Pérez Martín, Ester
author_facet	Pérez Martín, Ester Pérez Revuelta, Laura Barahona López, Cristina Pérez Boyero, David Alonso Peña, José Ramón Díaz López, David Weruaga Prieto, Eduardo
author_role	author
author2	Pérez Revuelta, Laura Barahona López, Cristina Pérez Boyero, David Alonso Peña, José Ramón Díaz López, David Weruaga Prieto, Eduardo
author2_role	author author author author author author
dc.subject.none.fl_str_mv	Endocannabinoids Microglia Neurodegeneration Neuroinflammation Neurotherapeutics Oleoylethanolamide (OEA) PCD mouse Purkinje cells Oleic Acids Animals PPAR alpha Cerebellum Endocannabinoids Anti-Inflammatory Agents Mice 2490 Neurociencias 2412 Inmunología cerebelo ácidos oleicos PPAR alfa animales ratones endocannabinoides antiinflamatorios
topic	Endocannabinoids Microglia Neurodegeneration Neuroinflammation Neurotherapeutics Oleoylethanolamide (OEA) PCD mouse Purkinje cells Oleic Acids Animals PPAR alpha Cerebellum Endocannabinoids Anti-Inflammatory Agents Mice 2490 Neurociencias 2412 Inmunología cerebelo ácidos oleicos PPAR alfa animales ratones endocannabinoides antiinflamatorios
description	[EN] Neurodegenerative diseases involve an exacerbated neuroinflammatory response led by microglia that triggers cytokine storm and leukocyte infiltration into the brain. PPARα agonists partially dampen this neuroinflammation in some models of brain insult, but neuronal loss was not the triggering cause in any of them. This study examines the anti-inflammatory and immunomodulatory properties of the PPARα agonist oleoylethanolamide (OEA) in the Purkinje Cell Degeneration (PCD) mouse, which exhibits striking neuroinflammation caused by aggressive loss of cerebellar Purkinje neurons. Using real-time quantitative polymerase chain reaction and immunostaining, we quantified changes in pro- and anti-inflammatory markers, microglial density and marker-based phenotype, and overall leukocyte recruitment at different time points after OEA administration. OEA was found to modulate cerebellar neuroinflammation by increasing the gene expression of proinflammatory mediators at the onset of neurodegeneration and decreasing it over time. OEA also enhanced the expression of anti-inflammatory and neuroprotective factors and the Pparα gene. Regarding microgliosis, OEA reduced microglial density-especially in regions where it is preferentially located in PCD mice-and shifted the microglial phenotype towards an anti-inflammatory state. Finally, OEA prevented massive leukocyte infiltration into the cerebellum. Overall, our findings suggest that OEA may change the environment to protect neurons from degeneration caused by exacerbated inflammation.
publishDate	2023
dc.date.none.fl_str_mv	2023 2026 2026
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10366/168676
url	http://hdl.handle.net/10366/168676
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	FPU16/04259 PID2019- 106943RB-I00 SA129P20 EDU/556/2019
dc.rights.none.fl_str_mv	Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	applicatio/pdf
dc.publisher.none.fl_str_mv	MDPI
publisher.none.fl_str_mv	MDPI
dc.source.none.fl_str_mv	reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca instname:Universidad de Salamanca (USAL)
instname_str	Universidad de Salamanca (USAL)
reponame_str	GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection	GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,812455

Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.

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