Cargando…

Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination

The endocannabinoid system is associated with protective effects in multiple sclerosis (MS) that involve attenuated innate immune cell responses. Astrocytes and microglia are modulated by endocannabinoids and participate in the biosynthesis and metabolism of these compounds. However, the role of neu...

Descripción completa

Detalles Bibliográficos
Autores principales: Moreno-García, Álvaro, Bernal-Chico, Ana, Colomer, Teresa, Rodríguez-Antigüedad, Alfredo, Matute, Carlos, Mato, Susana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563448/
https://www.ncbi.nlm.nih.gov/pubmed/32846891
http://dx.doi.org/10.3390/biom10091228
_version_ 1783595491232055296
author Moreno-García, Álvaro
Bernal-Chico, Ana
Colomer, Teresa
Rodríguez-Antigüedad, Alfredo
Matute, Carlos
Mato, Susana
author_facet Moreno-García, Álvaro
Bernal-Chico, Ana
Colomer, Teresa
Rodríguez-Antigüedad, Alfredo
Matute, Carlos
Mato, Susana
author_sort Moreno-García, Álvaro
collection PubMed
description The endocannabinoid system is associated with protective effects in multiple sclerosis (MS) that involve attenuated innate immune cell responses. Astrocytes and microglia are modulated by endocannabinoids and participate in the biosynthesis and metabolism of these compounds. However, the role of neuroglial cells as targets and mediators of endocannabinoid signaling in MS is poorly understood. Here we used a microfluidic RT-qPCR screen to assess changes in the expression of the main endocannabinoid signaling genes in astrocytes and microglia purified from female mice during the time-course of experimental autoimmune encephalomyelitis (EAE). We show that astrocytes and microglia upregulate the expression of genes encoding neurotoxic A1 and pro-inflammatory molecules at the acute disease with many of these transcripts remaining elevated during the recovery phase. Both cell populations exhibited an early onset decrease in the gene expression levels of 2-arachidonoylglycerol (2-AG) hydrolytic enzymes that persisted during EAE progression as well as cell-type-specific changes in the transcript levels for genes encoding cannabinoid receptors and molecules involved in anandamide (AEA) signaling. Our results demonstrate that astrocytes and microglia responses to autoimmune demyelination involve alterations in the expression of multiple endocannabinoid signaling-associated genes and suggest that this system may regulate the induction of neurotoxic and pro-inflammatory transcriptional programs in both cell types during MS.
format Online
Article
Text
id pubmed-7563448
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75634482020-10-27 Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination Moreno-García, Álvaro Bernal-Chico, Ana Colomer, Teresa Rodríguez-Antigüedad, Alfredo Matute, Carlos Mato, Susana Biomolecules Article The endocannabinoid system is associated with protective effects in multiple sclerosis (MS) that involve attenuated innate immune cell responses. Astrocytes and microglia are modulated by endocannabinoids and participate in the biosynthesis and metabolism of these compounds. However, the role of neuroglial cells as targets and mediators of endocannabinoid signaling in MS is poorly understood. Here we used a microfluidic RT-qPCR screen to assess changes in the expression of the main endocannabinoid signaling genes in astrocytes and microglia purified from female mice during the time-course of experimental autoimmune encephalomyelitis (EAE). We show that astrocytes and microglia upregulate the expression of genes encoding neurotoxic A1 and pro-inflammatory molecules at the acute disease with many of these transcripts remaining elevated during the recovery phase. Both cell populations exhibited an early onset decrease in the gene expression levels of 2-arachidonoylglycerol (2-AG) hydrolytic enzymes that persisted during EAE progression as well as cell-type-specific changes in the transcript levels for genes encoding cannabinoid receptors and molecules involved in anandamide (AEA) signaling. Our results demonstrate that astrocytes and microglia responses to autoimmune demyelination involve alterations in the expression of multiple endocannabinoid signaling-associated genes and suggest that this system may regulate the induction of neurotoxic and pro-inflammatory transcriptional programs in both cell types during MS. MDPI 2020-08-24 /pmc/articles/PMC7563448/ /pubmed/32846891 http://dx.doi.org/10.3390/biom10091228 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Moreno-García, Álvaro
Bernal-Chico, Ana
Colomer, Teresa
Rodríguez-Antigüedad, Alfredo
Matute, Carlos
Mato, Susana
Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination
title Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination
title_full Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination
title_fullStr Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination
title_full_unstemmed Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination
title_short Gene Expression Analysis of Astrocyte and Microglia Endocannabinoid Signaling during Autoimmune Demyelination
title_sort gene expression analysis of astrocyte and microglia endocannabinoid signaling during autoimmune demyelination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563448/
https://www.ncbi.nlm.nih.gov/pubmed/32846891
http://dx.doi.org/10.3390/biom10091228
work_keys_str_mv AT morenogarciaalvaro geneexpressionanalysisofastrocyteandmicrogliaendocannabinoidsignalingduringautoimmunedemyelination
AT bernalchicoana geneexpressionanalysisofastrocyteandmicrogliaendocannabinoidsignalingduringautoimmunedemyelination
AT colomerteresa geneexpressionanalysisofastrocyteandmicrogliaendocannabinoidsignalingduringautoimmunedemyelination
AT rodriguezantiguedadalfredo geneexpressionanalysisofastrocyteandmicrogliaendocannabinoidsignalingduringautoimmunedemyelination
AT matutecarlos geneexpressionanalysisofastrocyteandmicrogliaendocannabinoidsignalingduringautoimmunedemyelination
AT matosusana geneexpressionanalysisofastrocyteandmicrogliaendocannabinoidsignalingduringautoimmunedemyelination