title: Astrocyte-specific overexpressed gene signatures in response to methamphetamine exposure in vitro.
abstract: Astrocyte 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.
  
  
  
  We 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.
  
  
  
  We 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.
  
  
  
  Gene 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.
authors.affiliation: Cellular and Molecular Neurosciences Department, The Scripps Research Institute, La Jolla, CA, 92037, USA.|Anschutz Medical Campus, University of Colorado, Denver, CO, USA.
authors.forename: Nikki
authors.initials: N
authors.lastname: Bortell
authors.affiliation: Cellular and Molecular Neurosciences Department, The Scripps Research Institute, La Jolla, CA, 92037, USA.
authors.forename: Liana
authors.initials: L
authors.lastname: Basova
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, 92093, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Semenova
authors.affiliation: Department of Experimental Pharmacology, University of Nebraska Medical School, Omaha, NE, 68198, USA.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Fox
authors.affiliation: KAUST Environmental Epigenetic Program (KEEP), Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, 23955, Kingdom of Saudi Arabia.|Department of Medicine, Division of Genetic, University of California San Diego, 9500 Gilman Drive, La Jolla, California, 92093, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Ravasi
authors.affiliation: Cellular and Molecular Neurosciences Department, The Scripps Research Institute, La Jolla, CA, 92037, USA. cmarcond@scripps.edu.|Present address: San Diego Biomedical Research Institute, 10865 Road to the Cure, Suite 100 - San Diego, San Diego, CA, 92121, USA. cmarcond@scripps.edu.
authors.forename: Maria Cecilia G
authors.initials: MC
authors.lastname: Marcondes
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D053263:Gene Regulatory Networks / Q000187:drug effects* / Q000502:physiology; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008694:Methamphetamine
keywords: Astrocytes; Central nervous system; Methamphetamine; Systems biology