title: Effects of ethanol on immune response in the brain: region-specific changes in adolescent versus adult mice.
abstract: BACKGROUND
  Alcohol use occurs across the life span beginning in adolescence and continuing through adulthood. Ethanol (EtOH)-induced pathology varies with age and includes changes in neurogenesis, neurodegeneration, and glial cell activation. EtOH-induced changes in glial activation and immune activity are believed to contribute to EtOH-induced neuropathology. Recent studies indicate an emerging role of glial-derived neuroimmune molecules in alcohol abuse and addiction.
  
  
  METHODS
  Adolescent and adult C57BL/6 mice were treated via gavage with 6 g/kg EtOH for 10 days, and tissue was harvested 1 day post treatment. We compared the effects of EtOH on chemokine and cytokine expression and astrocyte glial fibrillary acidic protein (GFAP) immunostaining and morphology in the hippocampus, cerebellum, and cerebral cortex.
  
  
  RESULTS
  EtOH increased mRNA levels of the chemokine CCL2/MCP-1 in all 3 regions of adult mice relative to controls. The cytokine interleukin-6 (IL-6) was selectively increased only in the adult cerebellum. EtOH did not affect mRNA levels of the cytokine tumor necrosis factor-alpha (TNF-α) in any of these brain regions in adult animals. Interestingly, CCL2, IL-6, and TNF-α mRNA levels were not increased in the hippocampus, cerebellum, or cortex of adolescent mice. EtOH treatment of adult and adolescent mice resulted in increased GFAP immunostaining.
  
  
  CONCLUSIONS
  Collectively, these data indicate an age- and region-specific susceptibility to EtOH regulation of neuroinflammatory and addiction-related molecules as well as astrocyte phenotype. These studies may have important implications concerning differential alcohol-induced neuropathology and alcohol addiction across the life span.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Cynthia J M
authors.initials: CJ
authors.lastname: Kane
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Phelan
authors.forename: James C
authors.initials: JC
authors.lastname: Douglas
authors.forename: Gail
authors.initials: G
authors.lastname: Wagoner
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Johnson
authors.forename: Jihong
authors.initials: J
authors.lastname: Xu
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Phelan
authors.forename: Paul D
authors.initials: PD
authors.lastname: Drew
mesh_terms: D000375:Aging / Q000276:immunology* / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000187:drug effects* / Q000276:immunology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D000431:Ethanol / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007109:Immunity / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D008810:Mice, Inbred C57BL; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D002492:Central Nervous System Depressants; D018932:Chemokine CCL2; D018076:DNA, Complementary; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D012313:RNA
keywords: Adolescent; Adult; Astrocyte; CCL2; Neuroinflammation
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