title: Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia.
abstract: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature astrocytes. While previous work have been mostly focused on the neuronal fate of nestin-positive progenitors, in the present study, we sought to investigate in real time how nestin signals and cellular expression patterns are controlled in the context of neuroinflammatory challenge and ischemic brain injury.
  
  
  
  To visualize effects of neuroinflammation on neurogenesis/gliogenesis, we created a transgenic model bearing the dual reporter system luciferase and GFP under transcriptional control of the murine nestin promoter. In this model, transcriptional activation of nestin was visualized from the brains of living animals using biophotonic/bioluminescence molecular imaging and a high resolution charged coupled device camera. Nestin induction profiles in vivo and in tissue sections were analyzed in two different experimental paradigms: middle cerebral artery occlusion and lipopolysaccharide-induced innate immune stimuli.
  
  
  
  We report here a context- and injury-dependent induction and cellular expression profile of nestin. While in the baseline conditions the nestin signal and/or GFP expression was restricted to neuronal progenitors, the cellular expression patterns of nestin following innate immune challenge and after stroke markedly differed shifting the cellular expression patterns towards activated microglia/macrophages and astrocytes.
  
  
  
  Our results suggest that nestin may serve as a context-dependent biomarker of inflammatory response in glial cells including activated microglia/macrophages.
authors.affiliation: Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec, Canada.|Research Centre of Institut universitaire en santé mentale de Québec, 2601 Chemin de la Canardière, Quebec, Québec, G1J 2G3, Canada.
authors.forename: Senthil
authors.initials: S
authors.lastname: Krishnasamy
authors.affiliation: Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec, Canada.|Research Centre of Institut universitaire en santé mentale de Québec, 2601 Chemin de la Canardière, Quebec, Québec, G1J 2G3, Canada.
authors.forename: Yuan-Cheng
authors.initials: YC
authors.lastname: Weng
authors.affiliation: Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec, Canada.|Research Centre of Institut universitaire en santé mentale de Québec, 2601 Chemin de la Canardière, Quebec, Québec, G1J 2G3, Canada.
authors.forename: Sai Sampath
authors.initials: SS
authors.lastname: Thammisetty
authors.affiliation: Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec, Canada.|Research Centre of Institut universitaire en santé mentale de Québec, 2601 Chemin de la Canardière, Quebec, Québec, G1J 2G3, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Phaneuf
authors.affiliation: Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec, Canada.|Research Centre of Institut universitaire en santé mentale de Québec, 2601 Chemin de la Canardière, Quebec, Québec, G1J 2G3, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Lalancette-Hebert
authors.affiliation: Department of Psychiatry and Neuroscience, Faculty of Medicine, Laval University, Quebec, Canada. jasna.kriz@fmed.ulaval.ca.|Research Centre of Institut universitaire en santé mentale de Québec, 2601 Chemin de la Canardière, Quebec, Québec, G1J 2G3, Canada. jasna.kriz@fmed.ulaval.ca.
authors.forename: Jasna
authors.identifier: 0000-0002-1811-7456
authors.initials: J
authors.lastname: Kriz
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D008163:Luminescent Measurements / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000737:chemistry / Q000378:metabolism*; D057054:Molecular Imaging / Q000379:methods*; D064231:Nestin / Q000032:analysis / Q000378:metabolism*; D051381:Rats
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D064231:Nestin
keywords: Immune biomarkers; In vivo imaging; Inflammation; Microglia; Nestin; Stroke