Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro

Handle URI:
http://hdl.handle.net/10754/622994
Title:
Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro
Authors:
Bortell, Nikki; Basova, Liana; Semenova, Svetlana; Fox, Howard S.; Ravasi, Timothy ( 0000-0002-9950-465X ) ; Marcondes, Maria Cecilia G.
Abstract:
BackgroundAstrocyte activation is one of the earliest findings in the brain of methamphetamine (Meth) abusers. Our goal in this study was to identify the characteristics of the astrocytic acute response to the drug, which may be critical in pathogenic outcomes secondary to the use.MethodsWe developed an integrated analysis of gene expression data to study the acute gene changes caused by the direct exposure to Meth treatment of astrocytes in vitro, and to better understand how astrocytes respond, what are the early molecular markers associated with this response. We examined the literature in search of similar changes in gene signatures that are found in central nervous system disorders.ResultsWe identified overexpressed gene networks represented by genes of an inflammatory and immune nature and that are implicated in neuroactive ligand-receptor interactions. The overexpressed networks are linked to molecules that were highly upregulated in astrocytes by all doses of methamphetamine tested and that could play a role in the central nervous system. The strongest overexpressed signatures were the upregulation of MAP2K5, GPR65, and CXCL5, and the gene networks individually associated with these molecules. Pathway analysis revealed that these networks are involved both in neuroprotection and in neuropathology. We have validated several targets associated to these genes.ConclusionsGene signatures for the astrocytic response to Meth were identified among the upregulated gene pool, using an in vitro system. The identified markers may participate in dysfunctions of the central nervous system but could also provide acute protection to the drug exposure. Further in vivo studies are necessary to establish the role of these gene networks in drug abuse pathogenesis.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; KAUST Environmental Epigenetics Research Program (KEEP)
Citation:
Bortell N, Basova L, Semenova S, Fox HS, Ravasi T, et al. (2017) Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro. Journal of Neuroinflammation 14. Available: http://dx.doi.org/10.1186/s12974-017-0825-6.
Publisher:
Springer Nature
Journal:
Journal of Neuroinflammation
Issue Date:
9-Mar-2017
DOI:
10.1186/s12974-017-0825-6
Type:
Article
ISSN:
1742-2094
Sponsors:
TR is supported by KAUST. This work was performed with funding from the NIH/NIDA R01DA036164 to MCGM.
Is Supplemented By:
Bortell, N., Basova, L., Semenova, S., Fox, H., Ravasi, T., & Marcondes, M. (2017). Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro. Figshare. https://doi.org/10.6084/m9.figshare.c.3713953; DOI:10.6084/m9.figshare.c.3713953; HANDLE:http://hdl.handle.net/10754/624147
Additional Links:
http://link.springer.com/article/10.1186/s12974-017-0825-6
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorBortell, Nikkien
dc.contributor.authorBasova, Lianaen
dc.contributor.authorSemenova, Svetlanaen
dc.contributor.authorFox, Howard S.en
dc.contributor.authorRavasi, Timothyen
dc.contributor.authorMarcondes, Maria Cecilia G.en
dc.date.accessioned2017-03-15T07:15:26Z-
dc.date.available2017-03-15T07:15:26Z-
dc.date.issued2017-03-09en
dc.identifier.citationBortell N, Basova L, Semenova S, Fox HS, Ravasi T, et al. (2017) Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro. Journal of Neuroinflammation 14. Available: http://dx.doi.org/10.1186/s12974-017-0825-6.en
dc.identifier.issn1742-2094en
dc.identifier.doi10.1186/s12974-017-0825-6en
dc.identifier.urihttp://hdl.handle.net/10754/622994-
dc.description.abstractBackgroundAstrocyte activation is one of the earliest findings in the brain of methamphetamine (Meth) abusers. Our goal in this study was to identify the characteristics of the astrocytic acute response to the drug, which may be critical in pathogenic outcomes secondary to the use.MethodsWe developed an integrated analysis of gene expression data to study the acute gene changes caused by the direct exposure to Meth treatment of astrocytes in vitro, and to better understand how astrocytes respond, what are the early molecular markers associated with this response. We examined the literature in search of similar changes in gene signatures that are found in central nervous system disorders.ResultsWe identified overexpressed gene networks represented by genes of an inflammatory and immune nature and that are implicated in neuroactive ligand-receptor interactions. The overexpressed networks are linked to molecules that were highly upregulated in astrocytes by all doses of methamphetamine tested and that could play a role in the central nervous system. The strongest overexpressed signatures were the upregulation of MAP2K5, GPR65, and CXCL5, and the gene networks individually associated with these molecules. Pathway analysis revealed that these networks are involved both in neuroprotection and in neuropathology. We have validated several targets associated to these genes.ConclusionsGene signatures for the astrocytic response to Meth were identified among the upregulated gene pool, using an in vitro system. The identified markers may participate in dysfunctions of the central nervous system but could also provide acute protection to the drug exposure. Further in vivo studies are necessary to establish the role of these gene networks in drug abuse pathogenesis.en
dc.description.sponsorshipTR is supported by KAUST. This work was performed with funding from the NIH/NIDA R01DA036164 to MCGM.en
dc.publisherSpringer Natureen
dc.relation.urlhttp://link.springer.com/article/10.1186/s12974-017-0825-6en
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAstrocytesen
dc.subjectMethamphetamineen
dc.subjectCentral nervous systemen
dc.subjectSystems biologyen
dc.titleAstrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitroen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentKAUST Environmental Epigenetics Research Program (KEEP)en
dc.identifier.journalJournal of Neuroinflammationen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionCellular and Molecular Neurosciences Department, The Scripps Research Institute, La Jolla, CA 92037, USA.en
dc.contributor.institutionAnschutz Medical Campus, University of Colorado, Denver, CO, USA.en
dc.contributor.institutionDepartment of Psychiatry, University of California San Diego, San Diego, CA 92093, USA.en
dc.contributor.institutionDepartment of Experimental Pharmacology, University of Nebraska Medical School, Omaha, NE 68198, USA.en
dc.contributor.institutionDepartment of Medicine, Division of Genetic, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.en
dc.contributor.institutionSan Diego Biomedical Research Institute, 10865 Road to the Cure, Suite 100-San Diego, San Diego, CA 92121, USA.en
kaust.authorRavasi, Timothyen
dc.relation.isSupplementedByBortell, N., Basova, L., Semenova, S., Fox, H., Ravasi, T., & Marcondes, M. (2017). Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro. Figshare. https://doi.org/10.6084/m9.figshare.c.3713953en
dc.relation.isSupplementedByDOI:10.6084/m9.figshare.c.3713953en
dc.relation.isSupplementedByHANDLE:http://hdl.handle.net/10754/624147en
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