title: Determining the role of IL-4 induced neuroinflammation in microglial activity and amyloid-β using BV2 microglial cells and APP/PS1 transgenic mice.
abstract: BACKGROUND
  Microglia are considered the resident immune cells of the central nervous system (CNS). In response to harmful stimuli, an inflammatory reaction ensues in which microglia are activated in a sequenced spectrum of pro- and antiinflammatory phenotypes that are akin to the well-characterized polarization states of peripheral macrophages. A "classically" activated M1 phenotype is known to eradicate toxicity. The transition to an "alternatively" activated M2 phenotype encompasses neuroprotection and repair. In recent years, inflammation has been considered an accompanying pathology in response to the accumulation of extracellular amyloid-β (Aβ) in Alzheimer's disease (AD). This study aimed to drive an M2a-biased immune phenotype with IL-4 in vitro and in vivo and to determine the subsequent effects on microglial activation and Aβ pathology.
  
  
  METHODS
  In vitro, exogenous IL-4 was applied to BV2 microglial cell cultures to evaluate the temporal progression of microglial responses. In vivo, intracranial injections of an adeno-associate-virus (AAV) viral vector were performed to assess long-term expression of IL-4 in the frontal cortex and hippocampus of Aβ-depositing, APP/PS1 transgenic mice. Quantitative real-time PCR was used to assess the fold change in expression of biomarkers representing each of the microglial phenotypes in both the animal tissue and the BV2 cells. ELISAs quantified IL-4 expression and Aβ levels. Histological staining permitted quantification of microglial and astrocytic activity.
  
  
  RESULTS
  Both in vitro and in vivo models showed an enhanced M2a phenotype, and the in vivo model revealed a trend toward a decreased trend in Aβ deposition.
  
  
  CONCLUSIONS
  In summary, this study offers insight into the therapeutic potential of microglial immune response in AD.
authors.affiliation: Department of Physiology, University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, 40536, USA. clare.latta@student.manchester.ac.uk.|Department of Biology, The University of Manchester, Manchester, M13 9PL, UK. clare.latta@student.manchester.ac.uk.
authors.forename: Clare H
authors.initials: CH
authors.lastname: Latta
authors.affiliation: Department of Physiology, University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, 40536, USA. tlsudd2@uky.edu.
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Sudduth
authors.affiliation: Department of Physiology, University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, 40536, USA. emweek2@uky.edu.|Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA. emweek2@uky.edu.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Weekman
authors.affiliation: Department of Physiology, University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, 40536, USA. holly.brothers@uky.edu.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Brothers
authors.affiliation: Department of Physiology, University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, 40536, USA. erin.abner@uky.edu.|Department of Epidemiology, University of Kentucky, Lexington, KY, 40536, USA. erin.abner@uky.edu.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Abner
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, 40536, USA. gabriel.popa@uky.edu.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Popa
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, 40536, USA. michael.mendenhall@uky.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mendenhall
authors.affiliation: Department of Physiology, University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, 40536, USA. flor.gonzalez@uky.edu.|Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA. flor.gonzalez@uky.edu.
authors.forename: Floracita
authors.initials: F
authors.lastname: Gonzalez-Oregon
authors.affiliation: Department of Physiology, University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, 40536, USA. kaitlyn.braun@uky.edu.|Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA. kaitlyn.braun@uky.edu.
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: Braun
authors.affiliation: Department of Physiology, University of Kentucky, Sanders-Brown Center on Aging, Lexington, KY, 40536, USA. donna.wilcock@uky.edu.|Department of Physiology, University of Kentucky, Lexington, KY, 40536, USA. donna.wilcock@uky.edu.|University of Kentucky, Room 424 Sanders-Brown Center on Aging, 800 S Limestone Street, Lexington, KY, 40536, USA. donna.wilcock@uky.edu.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Wilcock
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002461:Cell Line, Transformed; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; C508853:PSEN1 protein, human; D053764:Presenilin-1; D049452:Green Fluorescent Proteins; D015847:Interleukin-4